B Lymphocyte Development

B Lymphocyte Development

• B cells are crucial components of the adaptive immune system, responsible for antibody production.
• B cell development involves distinct stages, each characterized by specific events, and changes in their expression of proteins.
• RAG-1, RAG-2, and TdT play vital roles in the rearrangement of heavy and light chains during B cell development.
• Allelic exclusion is critical in B cell rearrangement, preventing the expression of multiple antibody specificities from the same cell.
• Central and peripheral tolerance mechanisms ensure that the immune response does not target the body's own cells.
• Several types of B cells exist (immature, mature, naïve, virgin, B-1, B-2, activated, plasma, and memory B cells). Each has distinct characteristics.
• The B cell receptor complex comprises distinct components with specific functions.
• B cell activation and differentiation are driven by specific interactions and cytokines.
• Somatic recombination and somatic hypermutation lead to changes in antibody structure and affinity.
• T-dependent and T-independent B cell responses exhibit distinct characteristics.
• Surface markers on B cells provide functional and identification indicators. These markers help categorize different B cell types and stages of development.
• Mutations in RAG1 and/or RAG2 genes can result in severe combined immunodeficiency (SCID).
• B cell development involves a series of steps beginning in the bone marrow, where they differentiate and mature through distinct stages.

Acquired Immune System Development: Summary

• B cell development starts in the bone marrow.
• B cells migrate and mature in lymphoid organs and tissues.

Antibody Structure & Function

• Antibodies (immunoglobulins) have a general structure with antigen-binding sites and constant (Fc) regions.
• 5 Antibody Classes/Isotypes exist (IgG, IgM, IgD, IgA, IgE). Their class dictates their function and tissue distribution.
• Antibodies are crucial for the adaptive immune response, playing key roles in eliminating pathogens.

Immunoglobin Genes

• Immunoglobulins are generated through the rearrangement of multiple gene segments, leading to considerable diversity in antigen-binding specificity.
• The variability and diversity in B cell receptor arise via rearrangement of gene segments, ensuring broad adaptive responses to a wide range of antigens.

Adaptive Diversity

• Adaptive diversity is achieved through gene rearrangements.
• RAG-1 and RAG-2-mediated rearrangements of V, D, and J gene segments.

Omenn Syndrome

• Mutations of RAG1 and/or RAG2 genes result in severe combined immunodeficiency.
• Omenn Syndrome is characterized by a complete lack of circulating T and B cells. This is due to an early developmental blockage.

B Cell Development Stages

• The development of B cell maturation is characterized by surface marker expression and rearrangement of DNA components.

Elimination of Self-Reactive Clones

• Negative selection removes self-reactive B cells during development.
• Mechanisms like receptor editing and apoptosis eliminate potential damaging self-reactive B cells.
• Self-tolerance mechanisms ensure that the immune system does not attack the body's own components.

Peripheral Tolerance

• Not all self-antigens are present in the bone marrow.
• Peripheral tolerance is initiated when the self-reactive B cell encounters self-antigen in the periphery. Mechanisms include apoptosis or anergy.

The B Cell Receptor Complex

• The B cell receptor complex plays a vital role in B cell activation and signaling.
• Igα and Igβ associate with the B cell receptor to transmit intracellular signals.
• Other molecules, such as CD19, CD20, CD21, and CD81, are parts of the receptor complex. Their function is related to antigen recognition, intracellular signaling, and downstream cellular response in the case of proper activation by antigens.

B Cell Subsets

• B cells are categorized into subsets, such as B-1 cells and conventional B cells.
• Each B cell subset has unique characteristics and roles in the immune system.

B Cell Activation

• The B cell receptor (BCR) and co-receptor cooperate to activate B cells.
• CD19, CD21, and CD81 facilitate signaling events in B cells, leading to changes in gene expression and downstream cellular response.
• Post-activation events leading to plasma cells and memory cells are a later stage of development.

Activated B Cells

• Activated B cells differentiate into plasma cells or memory B cells.
• Plasma cells are antibody-producing factories, losing surface IgM and expression of MHC class II.
• Memory B cells are long-lived cells that mount rapid responses upon re-exposure to specific antigens.