IAS61 Specific Immune Reactivity Antibodies and Lymphocytes

B cells are responsible for producing immunoglobulins (antibodies) that recognize and bind to specific antigens, leading to their neutralization or destruction.

T cells are involved in recognizing and responding to infected or abnormal cells through their T cell receptors (TCRs), leading to the activation of immune responses that eliminate these cells.

Adaptive immunity is primarily driven by lymphocytes and their secreted products, which include antibodies and cytokines. Antibodies neutralize or destroy pathogens, while cytokines regulate and coordinate immune cell activity.

The innate immune system uses toll-like receptors (TLRs) to detect common microbial components such as carbohydrates, lipids, proteins, and nucleic acids. It recognizes invading microbes broadly through pattern recognition receptors.

The innate immune system broadly recognizes invading microbes and their products, while the adaptive immune system specifically recognizes antigens, which are unique structural features of particular microbes.

An antigen is a unique structural feature of a particular microbe or foreign molecule. It is significant in adaptive immunity as it allows for precise targeting, even among closely related microbes that may have different antigens.

• B cells mature in the Bone Marrow.
• T cells mature in the Thymus.

• Humoral immunity: Mediated by soluble proteins (antibodies) secreted by plasma cells, which are differentiated from B cells.
• Cell-mediated immunity: Mediated by the work of helper T cells and cytotoxic T cells.

B lymphocytes interact with antigens and differentiate into plasma cells that secrete antibodies, playing a crucial role in humoral immunity.

Helper T lymphocytes interact with microbial antigens presented by antigen-presenting cells, activating effector T lymphocytes and enhancing the immune response.

Cytotoxic T lymphocytes (CTL) interact with infected cells presenting microbial antigens and are responsible for the killing of infected cells.

1. Neutralization of microbes, phagocytosis, complement activation.
2. Activation of macrophages.
3. Inflammation.
4. Activation (proliferation and differentiation) of T and B lymphocytes.
5. Killing of infected cells.
6. Suppression of the immune response.

Antigens are recognized by a specific B cell receptor (BCR) or antibody and T cell receptor (TCR). The antigen that a given BCR/antibody or TCR recognizes is referred to as its cognate antigen.

T cells and B cells that have never been stimulated by their cognate antigen are called naïve T cells and naïve B cells.

BCR and antibodies can recognize antigens that are made of various macromolecules or small molecules.

T cell receptors (TCR) can mainly recognize peptide antigens displayed by major histocompatibility (MHC) molecules on antigen presenting cells or infected cells.

The three types of antigen presenting cells are dendritic cells, macrophages, and B cells.

Dendritic cells take up the antigen, present it with costimulators (e.g., B7) and CD28, leading to the activation of naive T cells, resulting in clonal expansion and differentiation into effector T cells.

Macrophages take up the antigen and present it to effector T cells, which then activate the macrophages, leading to cell-mediated immunity.

B cells take up the antigen, present it to effector T cells, which activate the B cells, leading to antibody production and humoral immunity.

NK cells are innate granular lymphocytes that exist in blood and lymph. They do not express antigen receptors.

NK cells induce cytotoxicity by coming in direct contact with virus-infected cells and delivering cytoplasmic granules into the infected cell to induce apoptosis.

Interferon-γ (IFN-γ) is secreted by NK cells to activate macrophages and regulate helper T cell function.

Immune cells can be found in several locations:

1. Blood & Lymph
2. Primary lymphoid organs (where lymphocytes are generated):
   • Bone marrow
   • Thymus
3. Secondary lymphoid organs (where antigens meet lymphocytes):
   • Lymph nodes
   • Spleen
   • Tonsils
   • Peyer's patches
4. Other tissues and organs (e.g., tissue resident macrophages/dendritic cells)

Lymphatics form a secondary drainage network that channels tissue fluid back into veins, collecting interstitial fluid, filtering it, and returning it to circulation.

Lymph nodes are located along lymphatic vessels and function as biological filters for tissue fluid (lymph), capturing and trapping antigens within these nodes.

Lymph nodes serve as antigen-collection and immune-activation sites, where antigens in lymph are captured and recognized by antigen-specific lymphocytes.

Naive T cells and naive B cells enter lymph nodes via arteries, reside until they encounter their specific antigen, and upon recognition, they become activated, undergo clonal proliferation, and initiate an immune response.

Immune cells can be found in the following locations:

1. Blood & Lymph
2. Primary lymphoid organs (where lymphocytes generate and mature):
   • Bone marrow
   • Thymus
3. Secondary lymphoid organs (where APC meets the lymphocyte):
   • Lymph nodes
   • Spleen
   • Tonsils
   • Peyer's patches
4. Other tissues and organs

1. Antigen Uptake: Antigen presenting cells (APCs) capture antigens through phagocytosis or endocytosis.

2. Processing: The captured antigens are processed into peptide fragments within the APC.

3. MHC Class II Loading: The processed peptides are loaded onto Major Histocompatibility Complex (MHC) Class II molecules.

4. Transport to Cell Surface: The MHC Class II-peptide complexes are transported to the surface of the APC.

5. T Cell Activation: The MHC Class II-peptide complex interacts with CD4+ T cells, leading to their activation.

TCR recognizes antigen peptides displayed on MHC molecules, which is crucial for T cell activation and response to pathogens.

CD3 is expressed by all T cells and is responsible for mediating TCR signaling, facilitating the activation of T cells upon antigen recognition.

CD4 and CD8 co-receptors determine the class of MHC molecule the T cell responds to; CD4+ T cells interact with MHC II, while CD8+ T cells interact with MHC I.

CD4-positive (CD4+) T cells are pre-determined to become helper T cells, while CD8-positive (CD8+) T cells are pre-determined to become cytotoxic T cells.

Class I MHC molecules are expressed on all nucleated cells and display peptides derived from protein antigens within the cytoplasm. They specifically target CD8+ T cells.

Class II MHC molecules are expressed only on professional antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells. They display peptides derived from extracellular protein antigens and specifically target CD4+ T cells.

Class I MHC molecules are expressed on all nucleated cells.

Class II MHC molecules are expressed on dendritic cells, macrophages (upon induction by IFN-y), and B cells, which are known as professional antigen presenting cells (APCs).

CD8+ T cells specifically interact with Class I MHC molecules that present peptides derived from cytoplasmic proteins.

CD4+ T cells specifically interact with Class II MHC molecules that present peptides derived from extracellular proteins.

In the Class I MHC pathway, proteins in the cytoplasm are processed into peptides by the proteasome, transported into the endoplasmic reticulum (ER) via TAP, and then bind to Class I MHC molecules. This complex is transported to the cell surface for presentation to CD8+ T cells.

In the Class II MHC pathway, extracellular proteins are internalized via endocytosis, degraded into peptides within endosomes/lysosomes, and Class II MHC molecules are synthesized in the ER with an invariant chain (Ii). The Ii is degraded in endosomes/lysosomes, allowing peptides to bind to Class II MHC molecules, which are then transported to the cell surface for presentation to CD4+ T cells.

Class I MHC molecules function like 'billboards' on the surface of all nucleated cells, displaying a sample of all proteins being made by the cell.

Cells infected by intracellular pathogens, such as viruses, display peptides derived from these pathogens on their Class I MHC molecules, signaling to cytotoxic T cells that they are infected.

When a cytotoxic T cell encounters a healthy cell displaying a peptide on its Class I MHC, it recognizes the cell as healthy and does not initiate an attack.

When a cytotoxic T cell detects an infected cell displaying a viral peptide on its Class I MHC, it recognizes the infection and may initiate an immune attack by releasing granzymes and perforins.

Dendritic cells capture microbial antigens from tissues and travel via lymphatic vessels to lymph nodes. During this journey, they mature and produce class I and II MHC molecules, which bind to antigen peptides processed from microbes and are presented on their surface.

At the lymph nodes, dendritic cells present the antigen-class II MHC complex to CD4+ T cells, leading to their activation.

Some dendritic cells can undergo cross-presentation, displaying antigens on their surface with class I MHC molecules for CD8+ T cells instead of class II MHC molecules for CD4+ T cells.

During their journey, dendritic cells mature and produce more class I and II MHC molecules, which are essential for presenting processed antigens to T cells.

Macrophages are derived from circulating monocytes or can be tissue-resident macrophages that self-renew from stem cells during embryonic development.

At resting state, macrophages express little to no class II MHC molecules.

IFN-γ causes macrophages to express class II MHC molecules, enabling them to present antigens to CD4+ T cells within infected tissues.

• Dendritic Cells (DC):

  • Not effective at killing pathogens.
  • Able to travel to lymph nodes.
  • Bring antigens from the site of infection to stimulate T cell proliferation and differentiation.

• Macrophages:

  • Effective at killing pathogens.
  • Unable to travel.
  • Primarily act at the site of infection to eliminate pathogens.

• CD4+ effector T cells:

  • Also known as helper T cells.

• CD8+ effector T cells:

  • Also known as cytotoxic T cells (CTLs).

Continual re-stimulation is important because it allows the immune response to be easily shut down when there are no more infections, preventing unnecessary immune activity.

T cells are re-stimulated through antigen presentation by activated macrophages or infected cells. CD8+ cytotoxic T cells interact with MHC I, while CD4+ helper T cells interact with MHC II.

MHC I is associated with CD8+ cytotoxic T cells, while MHC II is associated with CD4+ helper T cells.

T cells play a crucial role in cell-mediated immunity by recognizing and responding to infected or abnormal cells. They can directly kill infected cells, help activate other immune cells, and regulate immune responses.

T cell receptors (TCRs) are specialized proteins on the surface of T cells that recognize specific antigens presented by Major Histocompatibility Complex (MHC) molecules on the surface of other cells. This recognition is essential for T cell activation and subsequent immune response.

The primary immune response occurs when the immune system is exposed to an antigen for the first time, leading to a slower and weaker response. In contrast, the secondary immune response is faster and more robust due to the presence of memory cells that were generated during the primary response.

Activated naïve CD8+ T cells differentiate into cytotoxic T cells upon activation.

Cytotoxic T cells release perforins and granzymes to induce apoptosis in infected cells.

Perforin binds to the plasma membrane of target cells and forms a channel-like structure, allowing granzymes to enter and induce apoptosis.

Granzymes are serine proteases that enter target cells through perforin-formed channels and trigger apoptosis.

Helper T cells (Th cells) are activated naïve CD4+ T cells that produce various cytokines to regulate immune responses and inflammation. They do not produce all cytokines simultaneously but rather secrete a specific subset to coordinate an immune response against particular invaders.

The three major types of helper T cells are Th1, Th2, and Th17. They are classified based on their distinct profiles of cytokines that they produce, which dictate their specific roles in the immune response.

Dendritic cells (DC) carry antigens from intracellular pathogens to nearby lymph nodes and produce IL-12 in the process, which is crucial for the activation of Th1 cells.

Upon activation, Th1 cells produce Th1 cytokines including TNF, IFN-γ, and IL-2.

Th1 cells become activated at the site of infection through antigen presentation by macrophages via MHC II, leading to the release of Th1 cytokines at the infection site.

IFN-y promotes classical activation of macrophages (M1), leading to:

• Increased production of reactive oxygen/nitrogen species, enhancing the ability to kill microbes.
• Increased MHC II expression.
• Secretion of cytokines and chemokines.

IFN-y causes B cells to produce IgG through a process known as isotype switching.

TNF promotes classical activation of macrophages (M1), similar to the action of IFN-y.

IL-2 promotes the proliferation of Th1 cells, cytotoxic T cells, and NK cells.

Th2 cells produce IL-4, IL-5, and IL-13 cytokines.

IL-4 stimulates B cells to produce IgE, which activates mast cells, leading to allergic reactions and tissue repair.

IL-4 and IL-13 stimulate intestinal mucus secretion and peristalsis, helping to eliminate microbes and parasites from the gut.

IL-5 activates eosinophils, which play a crucial role in combating helminth infections and allergic responses.

Th2 cells, through IL-4 and IL-13, cause alternative activation of macrophages (M2), which aids in wound healing and the formation of scar tissue.

Th2 cells cause IgE production and mast cell activation, which leads to the release of histamine, contributing to allergic reactions.

Dendritic cells produce TGFβ, IL-6, and IL-23 during the invasion by extracellular pathogens, which lead to the activation of Th17 cells.

IL-17 is a chemokine that attracts a vast number of neutrophils and monocytes to the site of infection, enhancing the immune response.

IL-23 acts as a growth factor that stimulates the proliferation of Th17 cells, thereby enhancing their function in the immune response.

IL-21 causes B cells to produce IgG and IgA antibodies, facilitating isotype switching in the immune response.

At the end of the T cell-mediated immune response, cytotoxic T cells and Th cells are eliminated, leaving behind long-lived memory T cells.

Memory T cells can be rapidly induced to generate Th cells and cytotoxic T cells, resulting in larger responses than those generated by newly activated naïve T cells.

Memory T cells are significant because they provide a faster and more robust immune response upon re-exposure to the same antigen, compared to the response from naïve T cells.

B cells are responsible for producing immunoglobulins (antibodies) that recognize and bind to specific antigens. This binding leads to the neutralization of pathogens and the activation of other immune components, facilitating the elimination of the threat.

The primary immune response occurs when the immune system is first exposed to an antigen, leading to a slower and weaker response as B cells are activated and antibodies are produced. In contrast, the secondary immune response is faster and more robust due to the presence of memory B cells that were generated during the primary response, allowing for a quicker and more effective reaction upon re-exposure to the same antigen.

Naïve B cells express B cell receptors (BCR) but do not secrete antibodies.

After activation, naïve B cells differentiate into plasma cells which secrete antibodies (immunoglobulins).

BCR are cell membrane-bound immunoglobulins, while antibodies are immunoglobulins that are not bound to the cell membrane and are soluble in body fluid.

Secreted antibodies perform effector functions such as neutralization, complement fixation, and phagocyte binding.

An immunoglobulin monomer contains:

1. One pair of heavy chains
2. One pair of light chains These components are held together by disulfide bonds.

The Fab regions are the two identical "hands" of an immunoglobulin that bind to antigens.

An epitope is the specific region within an antigen that is bound by an immunoglobulin.

The Fc region is the constant region of an immunoglobulin that determines its isotype (IgA, IgD, IgE, IgG, and IgM) and its biological function.

The four groups of gene segments are V (variable), D (diversity), J (joining), and C (constant).

Immature B cells randomly select one of the V, D, and J segments to assemble a mature BCR heavy chain gene, enabling the generation of many different B cells that produce immunoglobulins with various Fab structures.

CD4+ Th cells express CD40L, which binds to CD40 on B cells, facilitating their activation.

B cells internalize protein antigens for processing and present them on MHC II to T cells, which is crucial for T cell recognition of the antigen.

After activation, Th cells secrete cytokines that further activate B cells, leading to their proliferation and differentiation into plasma cells that secrete antibodies.

Affinity maturation refers to the process where mutations occur in the immunoglobulin gene of plasma cells, allowing them to produce antibodies with higher affinity for the antigen.

The primary antibody class produced during the primary antibody response is IgM, with some isotype switching to IgG towards the later phase.

At the end of the primary antibody response, long-lived plasma cells (IgG-secreting) and memory B cells remain.

Upon repeated exposure, memory B cells are activated and readily generate IgG-secreting plasma cells, resulting in a faster and stronger response.

The typical lag time after immunization for the primary antibody response is usually 5-10 days.

The peak response of the secondary antibody response is larger compared to the smaller peak response of the primary response.

During the secondary response, there is a relative increase in IgG, and under certain situations, there may also be an increase in IgA or IgE due to antibody class (isotype) switching.

The typical lag time after immunization for the secondary antibody response is usually 1-3 days.

Naïve B cells can respond to polysaccharide or lipid antigens without the help of Th cells.

The presence of many repeated identical epitopes on polysaccharides and lipids causes the clustering of BCR, which is essential for B cell activation.

Other signals such as TLR (Toll-like receptor) ligands or complement proteins promote the T cell-independent response.

The T cell-independent pathway does not lead to antibody isotype switching and the formation of memory B cells.

Mainly IgM and low-affinity antibodies are produced, along with short-lived plasma cells.

The primary functions of antibodies include:

1. Neutralization: Antibodies bind to pathogens or toxins, preventing them from interacting with host cells.
2. Opsonization: Antibodies coat pathogens, enhancing their recognition and ingestion by phagocytes.
3. Complement Activation: Antibodies can activate the complement system, leading to the lysis of pathogens.
4. Agglutination: Antibodies can clump pathogens together, making it easier for immune cells to eliminate them.
5. Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies can recruit immune cells to destroy infected or cancerous cells.

B cells are responsible for producing antibodies (immunoglobulins) that specifically target and neutralize pathogens such as bacteria and viruses. They act as B cell receptors that recognize specific antigens, leading to the activation of the immune response.

1. Neutralize pathogens and toxins: Antibodies block the entry of microbes through epithelial barriers, prevent infection of cells by binding to pathogens, and inhibit the binding of toxins to cell receptors.

2. Promote activation of complement through classical pathway: Antibodies bind to antigens (microbes), initiating the classical pathway of complement activation, leading to the formation of C3 convertase and subsequent immune responses.

The Fab region of antibodies binds to microbial antigens, facilitating the recognition of microbes by the immune system.

The Fc region of antibodies binds to the Fc receptors on phagocytes, drawing microbes and phagocytes close together to enhance phagocytosis.

Antibodies opsonize microbes by binding to them, and this process works in synergy with complement proteins, which also opsonize microbes, enhancing their recognition and uptake by phagocytes.

NK cells stimulate antibody-dependent cellular cytotoxicity by recognizing IgG antibodies bound to infected or cancerous cells through the CD16 receptor. This process enhances the immune response against these cells.

Activating receptors on NK cells recognize cell surface molecules expressed by infected cells, cancer cells, or injured cells. This recognition is crucial for the activation of NK cells to eliminate these compromised cells.

MHC class I molecules are expressed by healthy host cells and bind to inhibitory receptors on NK cells. The loss of these molecules, such as during viral infections or certain cancers, is necessary for NK cell activation and subsequent killing of infected cells.

When inhibitory receptors on NK cells are engaged by MHC class I molecules, the NK cell is not activated and does not kill the target cell. Conversely, when these receptors are not engaged (e.g., in virus-infected cells with reduced MHC class I), the NK cell is activated and kills the infected cell.

Isotype switching is the process by which B cells change the isotype (or class) of antibody they produce from IgM to IgG, IgA, or IgE by altering the C gene segments.

Isotype switching changes the Fc region of the antibody produced by B cells, while the Fab region remains unchanged.

The different antibody isotypes produced during isotype switching include IgG, IgA, and IgE, transitioning from the initial IgM form.

B cell receptors for naïve B cells are membrane-bound IgM monomers.

Secreted IgM antibodies are pentamers, which are complexes of 5 monomers.

IgM antibodies are effective at:

1. Activating complement by the classical pathway
2. Neutralising pathogens and toxins

IgG antibodies can perform the following functions:

1. Neutralisation of pathogens/toxins
2. Opsonisation of pathogens
3. Promoting antibody-dependent cellular cytotoxicity by NK cells

IgG readily crosses the placenta, allowing it to pass from the mother's blood into the fetus' blood, thereby providing passive immunity and immune protection to the fetus.

IgG antibodies are monomers and have a characteristic 'Y' shape, consisting of:

• Light Chains on the top left and right corners
• Antigen Binding Region (Fab) closest to the light chains
• Heavy Chains forming the lower part of the 'Y'
• Fc Region at the tail end of the antibody molecule

IgA antibodies are dimers and are the main antibody class guarding the mucosal surfaces of the body. They are produced in response to microbes at mucosal barriers and are secreted into the milk of nursing mothers, providing passive immunity to the baby's intestinal mucosa.

IgE antibodies are monomers that activate mast cells in immune reactions against helminths and in allergic reactions such as anaphylaxis.

The primary immune response occurs when the immune system is first exposed to a specific antigen, leading to the production of antibodies and memory cells. This response is typically slower and less effective initially. In contrast, the secondary immune response happens upon subsequent exposures to the same antigen, resulting in a faster and more robust production of antibodies due to the presence of memory cells. This response is characterized by a higher concentration of antibodies and a quicker activation of the immune system.

The process is called VDJ recombination, which involves changes to the DNA encoding for antibodies or receptors in each cell as they develop.

Yes, all B cells and T cells start out with the same genomic DNA before undergoing changes to generate variations in antibodies and TCRs.

The diversity allows the immune system to specifically target and respond to a wide range of pathogens, including bacteria, viruses, and fungi.

V(D)J recombination is a process that occurs during the development of T cells and B cells in the thymus gland and bone marrow.

The BCR heavy chain loci in a B cell's chromosome contains four groups of gene segments: V, D, J, and C. Each B cell randomly selects one of the V, D, and J segments to assemble a mature BCR heavy chain gene.

The TCR alpha chain is formed by the recombination of V and J gene segments.

The TCR beta chain is formed by the recombination of V, D, and J gene segments.

Haematopoietic stem cells give rise to lymphocytes, each with a single type of receptor for a specific antigen, which are crucial for the adaptive immune response.

Lymphocytes that are reactive to 'self' antigens are eliminated by inducing apoptosis, which is essential to prevent inappropriate immune responses against normal cells.

Clonal selection involves the activation of a specific clone of naive lymphocyte by a foreign antigen, leading to its proliferation and differentiation into effector cells and long-lived memory cells.

Naive lymphocytes are those that can primarily react to foreign antigens, and they are crucial for initiating an immune response upon encountering a specific antigen.

The activation of a specific clone of naive lymphocyte leads to its proliferation and differentiation into effector cells, and potentially long-lived memory cells if Th cell-dependent activation occurs.

Memory T cells and memory B cells are long-lived cells that require continual stimulation. They are generated alongside effector lymphocytes, such as plasma cells, Th cells, and cytotoxic T cells. Unlike effector lymphocytes, which are eliminated by apoptosis after an infection is cleared, memory cells persist in the body and can mount a stronger immune response upon re-exposure to the same antigen.

After the eradication of the infection, effector lymphocytes are eliminated by apoptosis, while memory cells remain in the body to provide a quicker and stronger immune response if the same antigen is encountered again.

Memory cells are significant because they can rapidly react and mount a stronger immune response upon re-exposure to an antigen, providing long-term immunity and quicker protection against previously encountered pathogens.

Vaccination utilises the principle that a secondary immune response is usually much stronger and more rapid than a primary immune response.

Vaccines are generally made by:

1. Altering a whole pathogen or its toxin.
2. Generating a small protein component of the pathogen.

The aim is to reduce its virulent/toxic property, while still being able to generate a primary response.

Examples of vaccines include:

• Tetanus toxoid: altered form of toxin.
• BNT162b2 vaccine: mRNA of a mutated form of SARS-CoV2 spike protein.

Active immunity is induced by exposure to an antigen through either vaccination or infection.

Passive immunity occurs when antibodies are given to an individual through injection, pregnancy, or breast milk.

Passive immunity does not cause the generation of memory cells, while active immunity does.

Both active and passive immunity have specificity, meaning they target specific pathogens.

1. Antigen Uptake: Antigen presenting cells (APCs) capture antigens through phagocytosis or endocytosis.

2. Processing: The captured antigens are processed into peptide fragments within the APC.

3. MHC Class II Loading: The processed peptides are loaded onto Major Histocompatibility Complex (MHC) Class II molecules.

4. Transport to Cell Surface: The MHC Class II-peptide complex is transported to the surface of the APC.

5. T Cell Activation: The MHC Class II-peptide complex is recognized by CD4+ T cells, leading to their activation.

• B Cells: B cells are responsible for producing antibodies (immunoglobulins) that specifically target antigens.

• Immunoglobulins: These are glycoproteins that bind to specific antigens, neutralizing them or marking them for destruction by other immune cells.

• Memory B Cells: After activation, some B cells become memory B cells, which provide long-term immunity by responding more rapidly upon re-exposure to the same antigen.

• T Cells: T cells play a crucial role in cell-mediated immunity, targeting infected or cancerous cells.

• T Cell Receptors (TCRs): TCRs recognize specific antigens presented by MHC molecules on the surface of infected cells.

• Types of T Cells:

  • CD4+ T Cells: Help activate other immune cells, including B cells and CD8+ T cells.
  • CD8+ T Cells: Directly kill infected or cancerous cells.

• Acquired Immunity: This is the immunity developed after exposure to specific antigens, leading to a stronger and faster response upon re-exposure.

• Primary Immune Response:

  • Occurs upon first exposure to an antigen.
  • Takes longer to develop (days to weeks).
  • Produces a lower amount of antibodies.

• Secondary Immune Response:

  • Occurs upon subsequent exposures to the same antigen.
  • Develops more quickly (hours to days).
  • Produces a higher amount of antibodies due to memory cells.

The choice of C segments determines the isotype of an antibody and hence its biological functions.

V(D)J recombination is significant because it allows for the rearrangement of gene segments, leading to the production of diverse antibodies that can recognize a wide range of antigens.

Naïve B cells require the help of CD4+ Th cells to respond to protein antigens.

Naïve B cells bind part of the protein antigen through their B cell receptor (BCR).