B cell defects in SLP65/BLNK‐deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling

Open Access
Publisher Website
Google Scholar
Abstract
CD22 is an inhibitory coreceptor for B cell receptor (BCR) signaling. The inhibition is most likely mediated by activation of SHP‐1. We found that SLP65/BLNK reaches maximal tyrosine‐phosphorylation at earlier time points in CD22–/– than in wild type B cells upon BCR cross‐linking, suggesting that SLP65/BLNK is a substrate of SHP‐1. However, in contrast to the defective Ca2+ mobilization of SLP65/BLNK–/– B cells, there was a clear Ca2+ response in SLP65/BLNK×CD22 double‐deficient B cells. This implies that SLP65/BLNK is not the sole target of SHP‐1 in the regulation of the Ca2+ signaling strength. While SLP65–/– mice show several blocks of B cell differentiation, in SLP65/BLNK×CD22 double‐deficient mice the maturationblock of B cells in the spleen was partially rescued. However, the proliferative responses of B cells from both SLP65/BLNK–/– and double‐deficient mice were defective after IgM‐ or CD40‐stimulation. These results show that SLP65/BLNK is not absolutely essential for Ca2+ induction in B cells, because the deficiency of this adapter can be by‐passed by the additional deletion of an inhibitory receptor. Furthermore, these experiments suggest that B cell maturation in the spleen is directly dependent on the strength of BCR‐derived Ca2+ signals.