BCRsignalering

BCRsignalering refers to the cascade of intracellular events triggered when the B cell receptor engages its antigen. The BCR complex typically comprises membrane-bound immunoglobulin (usually IgM or IgD) associated with the signaling subunits CD79a (Igα) and CD79b (Igβ), which contain immunoreceptor tyrosine-based activation motifs ITAMs.

Engagement of antigen induces receptor clustering and activation of Src-family kinases such as Lyn, Fyn, or Blk, which phosphorylate the ITAMs on CD79a/b. This creates docking sites for Syk, a spleen tyrosine kinase, which is recruited and activated. Activated Syk propagates signals to downstream pathways including PLCγ2, leading to hydrolysis of PIP2 into IP3 and DAG, calcium mobilization, and PKCβ activation; concomitantly, PI3K is recruited and activated, contributing to Akt signaling.

Converging pathways activate transcription factors such as NF-κB, NFAT, and AP-1 via MAP kinases (ERK, JNK, p38), driving B cell proliferation, differentiation into plasma cells and memory B cells, and class-switch recombination. Signaling strength and duration are modulated by co-receptors (CD19-CD21-CD81) that amplify signals through PI3K, as well as inhibitory receptors such as CD22 and SHIP1 that dampen signaling to maintain tolerance.

Clinical relevance includes the association of dysregulated BCR signaling with autoimmune diseases and B-cell malignancies. Therapeutic targeting comprises Bruton's tyrosine kinase inhibitors (ibrutinib), PI3K inhibitors (idelalisib), and Syk inhibitors (fostamatinib).