BCR Activation Signal

B cell receptors (BCR) are activated when they come in contact with their matching antigen. The BCR intracellular ITAMs on the alpha and beta chains are phosphorylated by Fyn, Byk, and Lyn. Co-receptors for B cells include CD19, CD21, and CD81. Phosphorylation of CD19’s intracellular portion recruits Src family kinases and signaling through the B cell receptor and recruitment of PI3K. Syk is recruited to the phosphorylated ITAM. Syk phosphorylates the scaffold BLNK (SLP-65). Btk activates PLC-gamma which then hydrolyzes PIP2 into DAG and IP3. IP3 leads to Ca2+ signaling and DAG leads to signaling of transcription factors similar to T cells. PKC is activated by DAG and Ca2+ which in turn activates NFkB. Small G protein can activate MAPK cascades leading to Fos and AP-1 activation. Ca2+ activates calcineurin which activates NFAT. Net result of activating NFkB, NFAT, and AP-1 which lead to cell proliferation and differentiation.

Secondary Activation Signal

Once in contact with its antigen the cell engulfs the antigen and processes it for presentation in a MHC II molecule. This molecule is presented to CD4+ T cells which then provides a second activation of the B cell. This secondary activation can also be T cell independent (Thymus independent activation). In this case the secondary signal is provided by bacterial wall components. After the second activation the B cells begins proliferating and forms a germinal center.

Germinal Centers

These are the place where B cells undergo affinity maturation. In the dark zone are centroblasts which rapidly proliferate and undergo somatic mutations and undergo class switching. They undergo selection by Tfh and follicular dendritic cells. The maturing B cells progress to the light zone where they are considered centrocytes and express their antibody on the surface. Tfh and follicular dendritic cells give survival signals to Bs baised on their antibody affinity for the antigen. Thus choosing those Bs that acquired mutations that resulted in higher affinity. These selected cells then progress back to the dark zone to further proliferate and affinity maturate. If recieve differentation signal mature Bs leave the germinal center and become plasma cells that secrete antibody or memory B cells.