B cells are crucial players in our immune system, developing from stem cells in bone marrow. They undergo a complex maturation process, creating unique receptors to recognize specific antigens. This diversity allows our bodies to defend against a wide range of pathogens.

B cell activation can be T-dependent or T-independent, leading to antibody production. Primary and secondary antibody responses differ in speed and effectiveness. Clonal selection, affinity maturation, and class switching fine-tune our immune defenses, making them more potent over time.

B Lymphocyte Development and Activation

Development of B cells

• B cells originate from hematopoietic stem cells in the bone marrow
  • Stem cells differentiate into common lymphoid progenitor cells which give rise to various lymphocyte lineages
  • Progenitor cells further differentiate into pro-B cells, the earliest stage of B cell development
• Pro-B cells undergo V(D)J recombination to generate unique B-cell receptors (BCRs)
  • Recombination of variable (V), diversity (D), and joining (J) gene segments creates vast diversity in antigen recognition
  • Successful recombination leads to the formation of pre-B cells expressing a functional pre-BCR
• Pre-B cells express surface IgM and differentiate into immature B cells
• Immature B cells undergo negative selection to eliminate self-reactive cells
  • Cells that bind strongly to self-antigens are eliminated through apoptosis or undergo receptor editing to change their specificity
• Surviving immature B cells migrate to secondary lymphoid organs (spleen, lymph nodes) where they mature into naïve B cells
  • Further maturation into mature, naïve B cells expressing both surface IgM and IgD as antigen receptors

B-cell vs T-cell receptors

• B-cell receptors (BCRs) are membrane-bound immunoglobulins (antibodies)
  • Composed of two heavy chains and two light chains forming a Y-shaped structure
  • Antigen-binding site formed by the variable regions of heavy and light chains determines specificity
  • Recognize and bind to specific epitopes on soluble antigens in their native conformation
• T-cell receptors (TCRs) are heterodimeric protein complexes
  • Composed of an α chain and a β chain (or γ and δ chains in a minority of T cells)
  • Antigen-binding site formed by the variable regions of α and β chains interacts with peptide-MHC complexes
  • Recognize and bind to peptide antigens presented by MHC molecules on antigen-presenting cells (APCs)
• BCRs can directly bind to native antigens, while TCRs require processed peptide antigens presented by MHC for recognition

B Cell Activation and Antibody Response

T-dependent vs T-independent activation

• T-dependent B cell activation requires interaction with helper T cells
  1. B cells internalize and process antigen bound to BCRs
  2. Processed antigen is presented on MHC class II molecules to helper T cells
  3. Activated helper T cells provide co-stimulatory signals (CD40L) and cytokines to stimulate B cell activation and differentiation
  • Leads to the formation of germinal centers, affinity maturation, and memory B cell development
• T-independent B cell activation occurs without the involvement of helper T cells
  • Type 1 T-independent antigens (lipopolysaccharide) directly activate B cells through pattern recognition receptors (TLRs)
  • Type 2 T-independent antigens (polysaccharides) crosslink multiple BCRs, providing strong activation signals
  • T-independent activation leads to rapid antibody production, primarily IgM, without memory B cell formation

Primary vs secondary antibody responses

• Primary antibody response occurs upon first exposure to an antigen
  • Characterized by a lag phase (7-10 days) before antibody production begins as naïve B cells become activated
  • Predominantly produces IgM antibodies with lower affinity binding to the antigen
  • Generates memory B cells specific to the antigen for future encounters
• Secondary antibody response occurs upon subsequent exposure to the same antigen
  • Characterized by a shorter lag phase (1-3 days) and a more rapid and robust antibody production due to memory B cells
  • Predominantly produces high-affinity IgG antibodies, with some IgA and IgE for enhanced antigen clearance
  • Memory B cells quickly differentiate into plasma cells, leading to a faster and stronger response compared to the primary response
• Secondary response exhibits higher antibody titers, improved antibody affinity, and a more rapid clearance of the antigen

Clonal Selection and Affinity Maturation

• Clonal selection theory explains how B cells specific to an antigen are selected for expansion
  • Only B cells with receptors that bind to the antigen are activated and proliferate
  • This process results in the production of antibody-secreting plasma cells and memory B cells
• Affinity maturation improves antibody affinity over time
  • Somatic hypermutation introduces mutations in the variable regions of antibody genes
  • B cells with higher affinity antibodies are preferentially selected for survival and expansion
• Class switching allows B cells to produce different antibody isotypes (IgG, IgA, IgE) while maintaining antigen specificity
  • This process enhances the versatility of the antibody response

Complement System and Effector Functions

• The complement system enhances antibody-mediated immunity (antibody-mediated immunity)
  • Antibodies can activate the classical complement pathway
  • Complement proteins aid in pathogen elimination through various mechanisms
• Opsonization is a process where antibodies coat pathogens, making them more easily recognized and engulfed by phagocytes