HUMORAL IMMUNE RESPONSE

Specific antigen Stimulation gives--Specific antibody production by a B cell (Clonal Selection) Stimulation---------------------Proliferation------------------Differentiation (plasma Cells or memory cells) B-Cell Antigen Receptor (BCR) In clonal selection, B cell recognizes antigen This is accompanied by differential RNA splicing yielding 2 forms of Ig H chain A secreted form A membrane form Ig H combines with L chain to make membrane form Membrane Ig is retained in ER unless it can associate with transmembrane proteins Ig- and Ig- Ig- and Ig- proteins associate with membrane Ig to form B-cell antigen receptor (BCR) BCR is responsible for signaling events that inform the B cell on contact with antigen T-Independent Antigens (TI) Generally------Ag + BCR No B activation Because most protein Ags require T cell help for Ab production TI Ag do not require T cell help TI- Ag divided into 2 groups TI-1 (LPS) TI-2 (bacterial flagella) TI-1 Polyclonal B cell activators, both specific and non-specific B cells B cells primarily through non-immunoglobulin receptors Also stimulate MQ resulting in cytokine production (IL-1, TNF-a) At low conc. TI-1 Ag tend to be B cell specific

TI-2 Non-polyclonal B cell activation Do not activate MQ either Are highly repetitive polymeric Ag e.g polysaccharides from bacterial cell walls bacterial flagella etc Activate B cells by X-linking BCR molecules giving intense prolonged B-cell signaling Low-level cytokine required for activation T-cell help and accessory signals Most protein Ag induce Ab response in presence of helper T cells T cell help provided by: Cytokines (IL-4, IL-5) Cell-cell contact i.e surface protein between Th and B cells like B-cell protein CD40 T-cell protein ligand CD40L-which appears only after T-cell activation Sometimes B cells activated without Ag by: CD40L and IL-4 and IL-5 Other times CD40L contact without Ag leads to B cell apoptosis Generally Ag binding plus CD40L act synergistically to trigger B-cell activation Accessory molecules that send signals to activate B cells when they combine their ligands are: CD22 Complement receptors Class II MHC proteins In contrast activation suppressed when: Antigen/antibody complexes bind to B-cell surface Fc receptorsthus negative feed back for B-cell response

Other molecules that modulate B-cell activation are: CD45 membrane glycoprotein CD45 found on all hematopoetic cells Exact role of CD45 not known But CD45 stimulates BCR and TCR signaling Antigen presentation by B lymphocytes Ag presenting cells: B cells MQ Dendritic cells Activation of B cells by T-cell dependent Ag require direct contact btwn the cells B cells present Ag to Th cells in association with MHC II B cells poor at Ag uptake by phagocytosis and pinocytosis (cf MQ, Dendritic cells) B cells take Ag via BCR Bound Ag internalized thru receptor-mediated endocytosis (Ig) Ag processed in endosomes IL-4, specific Ag, Polyclonal B cell activators all upregulate MHC synthesis In addition to CD40, B cells express B7.1 and B7.2 protein costimulators In addition BCR stimulates increased expression of MHC II It also induces expression of B7.1 and B7.2 It also enhances cell-cell adhesion If no costimulation is present, B cell presentation of Ag leads to their inactivation Activated Th cells can provide help to B cells even if no costimulatory molecules present Cytokines secreted by Activated B cells that increase Th cell activation: IL-6 TNF-a

Limitations of B cells as Ag Presenters Not present in large numbers at most sites in the body Limited phagocytic capacity Unimmunized persons have rare few B cells specific for an Ag