B Cell Activation Overview

B Cell Activation

• B cell activation occurs in two ways: T-independent and T-dependent.
• T-independent activation involves binding of polysaccharides to B cell receptors (surface IgD and IgM), and complement receptors (CD21, CD35). An example is Haemophilus influenzae B.
• In T-dependent activation, B cells bind to the antigen using B cell receptors (surface IgD & IgM).
• The B cell presents the antigen with MHC II complex to activate the CD4 T cells.
• CD80/86 molecule on B cells bind with CD28 on T helper 2 cell.
• CD40 molecule on B cells bind with CD40L on T helper 2 cell.

Cytokines and B cell proliferation and differentiation

• T helper 2 cells produce IL-4, IL-5, IL-6 and IL-13.
• B cells proliferate and differentiate into B memory cells and plasma cells that produce and secrete IgM (primary immune response).
• On re-exposure, memory B cells rapidly differentiate into plasma cells producing more IgM, IgG, and IgA (secondary immune response).

Primary and Secondary Immune Responses

Immunoglobulins (Antibodies)

• Immunoglobulins (Ig) are glycoproteins that mediate humoral immunity.
• They are produced by plasma cells and exist as membrane-bound immunoglobulins (IgM & BCR) and secreted immunoglobulins.
• There are five classes of immunoglobulins: three major classes (IgG, IgM, IgA) and two minor classes (IgD and IgE).

Immunoglobulin Structure

• Four polypeptide chains form a Y-shaped molecule held together by disulfide bonds.
• Two identical light chains, either kappa or lambda.
• Two identical heavy chains with one V domain (VH) and three or four C domains (CH1, CH2, CH3, and CH4).
• The VL and VH domains form a pocket that constitutes the antigen binding site.

Immunoglobulin Functions

• Block binding of microbes or toxins to cells.
• Opsonization and phagocytosis.
• Antibody-dependent cellular cytotoxicity (ADCC).
• Activation of the classical pathway of complement by IgG and IgM.

Complement System

• Circulating and membrane-associated proteins that function in both innate and adaptive immunity.
• Synthesized in the liver in an inactive form.
• Includes components C1 to C9 and factors B, D, & P.

Complement Pathways

• Classical pathway: Activated by antigen-antibody complexes (IgM & IgG).
• Mannan-binding lectin pathway: MBLs bind to specific mannose residues on microbes and activate MBL-activated serine proteases (MASP1 & MASP2).
• Alternative pathway: Bacterial endotoxin (LPS) directly produces spontaneous breakdown of C3 (C3a & C3b).

Complement Functions

• Complement-mediated lysis: The membrane attack complex (MAC) creates pores in cell membranes, inducing osmotic lysis.
• Opsonization and phagocytosis: C3b or C4b act as opsonins, enhancing phagocytosis by binding to microbes.
• Mediators of inflammation and chemo-attractants: C3a, C4a, and C5a act as mediators of inflammation and chemo-attractants to phagocytes.

Clinical Uses of Cytokines

• IL-2: Renal cell cancer and metastatic melanoma
• IL-11: Treatment of thrombocytopenia
• G-CSF: Bone marrow recovery from inhibition
• GM-CSF: Bone marrow recovery from inhibition
• Erythropoietin: Anemia with renal failure

Study Questions

• Classical complement pathway: Initiated by the formation of antigen-antibody complexes.
• Alternative complement pathway: Initiated by lipopolysaccharides (LPS) of Gram-negative bacteria.