BCRS

B cell receptors (BCRs) are membrane-bound immunoglobulins that enable B cells to detect specific antigens. Each BCR consists of a membrane-bound antibody molecule (the heavy and light chain variable regions responsible for antigen binding) associated with a signaling complex formed by the Igα (CD79a) and Igβ (CD79b) subunits. Upon antigen binding, the ITAMs in Igα/Igβ are phosphorylated by Src-family kinases, initiating a signaling cascade that activates the B cell.

BCR diversity arises from V(D)J recombination during B cell development, generating a vast repertoire of antigen-binding specificities. Additional junctional diversification and the pairing of different heavy and light chains expand this diversity. Central tolerance in the bone marrow and peripheral tolerance help eliminate or inactivate self-reactive B cells to prevent autoimmunity.

Functionally, BCR engagement leads to B cell activation, clonal expansion, and differentiation into plasma cells or memory B cells. Activated B cells internalize bound antigen, process it, and present peptide fragments on MHC class II molecules to helper T cells, receiving help for germinal center reactions. Co-receptors such as CD19, CD21, and CD81 modulate signaling strength and sensitivity, lowering the threshold for activation.

In germinal centers, B cells undergo somatic hypermutation and class switch recombination, driven by the enzyme activation-induced cytidine deaminase (AID). This leads to higher-affinity antibodies and a switch from IgM/IgD to other isotypes such as IgG, IgA, or IgE, conferring different effector functions.

Clinical relevance includes diseases with altered BCR signaling or B cell development; therapies targeting BCR signaling pathways or B cell markers are used to treat various B cell–related conditions.