B Cell Receptor Signaling Pathway

B cells mediate the humoral immune response, one component of the activity of the adaptive immune system. B cells have several receptors which transduce external signals and influence the fate of the B cell. Nevertheless, the principal signaling pathway in B cell activity is the B Cell Antigen-Receptor (BCR) pathway. There are several possible responses that could be signaled in a B cell, such as proliferation, apoptosis, and differentiation into memory B cells or B cells that produce antibodies. Each B cell has receptors which are specific to a certain antigen. If a B cell never binds with its antigen, it will finally undergo apoptosis. Upon antigenation of the B cell, the immune response will be triggered and the B cell will differentiate and proliferate.

Normal B cells receive two types of signals from their BCRs. The first one - known as tonic - occurs in the absence of external ligands. Currently, it is believed that quiescent, circulating and mature B-cells depend on signals constantly generated by functional BCR. Removal of the BCR from a B-cell leads to accelerated apoptosis, which indicates that tonic BCR signaling is required for normal B-cell survival. The second type of signal - referred to as antigen-dependent - is generated by binding of an external antigen to the BCR and results in the clustering and activation of a signaling complex that transmits the signal inside the cell. In brief, BCR signaling pathways are modulated by BCL6 in germinal center and as a consequence B cells with high-affinity receptors are selectively expanded.

The complex signaling responsible for the activation of B cells has been studied widely. With the identification of a large number of proteins responsible for signal transduction came the observation that many of these processes are tightly regulated in normal B cells and are aberrantly activated in select B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). This knowledge has allowed for the development of inhibitors of the B-cell receptor (BCR) pathway, which has shown promising early clinical activity in refractory CLL and NHL. Moreover, it is possible that CLL and different types of NHL will have divergent ideal targets based on their specific disease biology. The dramatic change in treatment landscape driven by the introduction of targeted therapy with imatinib in chronic myeloid leukemia (CML) followed by second-generation molecules with further improved properties provides great excitement of the potential of similar approaches in CLL, although the considerable genetic heterogeneity in CLL will likely mean that multiple drugs or multitargeted agents are necessary.

Creative Biogene is able to offer a series of B cell receptor signaling pathway related products including stable cell lines, viral particles and clones for your drug discovery projects.

B Cell Receptor Signaling Pathway Product Panel

AKT1	AKT2	BCL10	CHUK	FOS	GRB2
GSK3B	IFITM1	IKBKB	IKBKG	INPPL1	JUN
KRAS	MALT1	MAP2K1	MAP2K2	MAPK1	MAPK3
NFATC1	NFKB1	NFKBIA	NRAS	PIK3R1	PIK3R2
PIK3R3	PPP3CC	RAF1	RELA	VAV1	VAV3

References:

Merolle M I, et al. The B cell receptor signaling pathway in mantle cell lymphoma. Oncotarget, 2018, 9(38).
ojarczuk K, et al. B-cell receptor signaling in the pathogenesis of lymphoid malignancies. Blood Cells Molecules & Diseases, 2015, 55(3):255-265.
Woyach J A, et al. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood, 2012, 120(6):1175-1184.

* For research use only. Not intended for any clinical use.

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