Editors' ChoiceImmunology

Receptor cooperation in B cells

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Sci. Signal.  23 May 2017:
Vol. 10, Issue 480, eaan7951
DOI: 10.1126/scisignal.aan7951

TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor.

In innate immune cells, members of the Toll-like receptor (TLR) family recognize microbial products and stimulate cytokine production as part of the immune response. However, the activation of TLRs in B cells stimulates their proliferation and differentiation into antibody-secreting cells. B cell proliferation and differentiation are also stimulated by the antigen-mediated activation of the B cell receptor (BCR), which signals through the tyrosine kinase Syk. Schweighoffer et al. found that Syk was also required to mediate TLR4-stimulated B cell activation. Compared with wild-type cells, Syk-deficient mouse B cells showed reduced survival and proliferation in response to the TLR4 agonist lipopolysaccharide (LPS). Syk was also required for the LPS-stimulated secretion of the cytokines interleukin-10 (IL-10) and tumor necrosis factor (TNF) by B cells. LPS stimulated the phosphorylation (and thus activation) of Syk in wild-type B cells, which required the BCR. Indeed, compared to wild-type B cells, BCR-deficient B cells showed markedly reduced proliferation in response to LPS, as well as the reduced cell surface expression of activation markers. Loss of the TLR4-associated adaptor molecule MyD88 had no effect on the ability of LPS to stimulate Syk phosphorylation; however, LPS-induced activation of the transcription factor nuclear factor κB (NF-κB) was inhibited. Together, these data suggest that TLR4 signaling activates two separate pathways in B cells. The first involves the MyD88-depdendent activation of NF-κB, whereas the second leads to the BCR-dependent stimulation of Syk, which is required for B cell activation. Further mechanistic insight into how these two receptors cooperate to activate Syk in B cells remains to be discovered.

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