B Cell Activation Overview

Study Notes

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.

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).

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).

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.

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.

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-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.

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