Abstract
CD23 has been implicated as a negative regulator of IgE and IgG antibody responses. However, whether CD23 has any role in B-cell activation remains unclear. We examined the expression of CD23 in different subsets of peripheral B cells and the impact of CD23 expression on the early events of B-cell receptor (BCR) activation using CD23 knockout (KO) mice. We found that in addition to marginal zone B cells, mature follicular B cells significantly down regulate the surface expression level of CD23 after undergoing isotype switch and memory B-cell differentiation. Upon stimulation with membrane-associated antigen, CD23 KO causes significant increases in the area of B cells contacting the antigen-presenting membrane and the magnitude of BCR clustering. This enhanced cell spreading and BCR clustering is concurrent with increases in the levels of phosphorylation of tyrosine and Btk, as well as the levels of F-actin and phosphorylated Wiskott Aldrich syndrome protein, an actin nucleation promoting factor, in the contract zone of CD23 KO B cells. These results reveal a role of CD23 in the negative regulation of BCR signaling in the absence of IgE immune complex and suggest that CD23 down-regulates BCR signaling by influencing actin-mediated BCR clustering and B-cell morphological changes.
Highlights
CD23 has been studied for more than two decades, its immunological function is not fully understood
This study reveals a role for CD23 in the negative regulation of BCR signaling induced by stimulation of membrane-associated antigen and soluble antigen
Since the inhibitory effect of CD23 was observed in the absence of IgE-immune complexes, this indicates that CD23 can exert its negative regulatory function without being crosslinked and colligated with the BCR
Summary
CD23 has been studied for more than two decades, its immunological function is not fully understood. BCR clustering is concurrent with the morphological changes of B cells: spreading followed by contraction, when interacting with antigen presented on the cell membrane and immobile surface[14] These early events depend on BCR proximal signaling and signaling-induced actin reorganization, and are regulated by the binding affinity of the BCR to antigen and the density of antigen on the presenting surface[15]. BCR central clusters, the coalescent product of BCR microclusters, recruit the inhibitory phosphatase SHIP-1, leading to the down regulation of BCR signaling at the cell surface[17]. We have shown that actin remodeling is critical for the initiation and regulation of the early events of BCR signaling[17,18] by controlling the lateral mobility of surface BCRs and B-cell morphology. B cell contraction promotes the coalescence of BCR microclusters into a central cluster, which leads to the attenuation of surface signaling[17,20]
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