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Publication : CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes.

First Author  Dasu T Year  2009
Journal  Mol Immunol Volume  46
Issue  13 Pages  2655-65
PubMed ID  19541367 Mgi Jnum  J:151717
Mgi Id  MGI:4355106 Doi  10.1016/j.molimm.2009.04.015
Citation  Dasu T, et al. (2009) CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes. Mol Immunol 46(13):2655-65
abstractText  B-1 cells reside predominantly within the coelomic cavities, tonsils, Peyer's patches, spleen (a minor fraction - approximately 5%) and are absent in the lymph nodes. They are the primary sources of natural IgM in the body. B-1 cells express polyreactive B cell receptors (BCRs) that cross react with self-antigens and are thus implicated in auto-immune disorders. Previously, we reported that peritoneal B-1 cells are deficient in CD19-mediated intracellular signals leading to Ca(2+) mobilization. Here, we find that splenic B-1 cells, like peritoneal B-1 cells, are defective in Ca(2+) release upon B cell activation by co-cross-linking BCR and CD19. In the absence of extracellular sources of Ca(2+), intracellular Ca(2+) flux is similar between B-1 and B-2 cells. Moreover, the intracellular component of Ca(2+) release in both subsets of B cells is mostly PI3K dependent. BCR and CD19 co-cross-linking activates Akt, a key mediator of survival and proliferation signals downstream of PI3K in splenic B-2 cells. Splenic B-1 cells, on the other hand, do not phosphorylate Akt (S473) upon similar treatment. Furthermore, BCR+CD19 cross-linking induced phosphorylation of JNK is much reduced in splenic B-1 cells. In contrast, B-1 cells exhibited increased levels of constitutively active pLyn which appears to have an inhibitory role. The CD19 induced Ca(2+) response and BCR induced proliferation response were restored by a partial inhibition of pLyn with Src kinase specific inhibitors. These findings suggest a defect in CD19-mediated signals in both peritoneal and splenic B-1 B lymphocytes, which is in part, due to higher levels of constitutively active Lyn.
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