| First Author | Tang H | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 2 | Pages | 570-580 |
| PubMed ID | 28615414 | Mgi Jnum | J:251379 |
| Mgi Id | MGI:6099685 | Doi | 10.4049/jimmunol.1700109 |
| Citation | Tang H, et al. (2017) Loss of IP3 Receptor-Mediated Ca(2+) Release in Mouse B Cells Results in Abnormal B Cell Development and Function. J Immunol 199(2):570-580 |
| abstractText | Intracellular calcium (Ca(2+)) mobilization after engagement of the BCR has been proposed to play an important role in B cell development and function. BCR activation causes an initial Ca(2+) release from the endoplasmic reticulum that is mediated by inositol 1,4,5-trisphosphate receptor (IP3R) and then triggers store-operated Ca(2+) entry once endoplasmic reticulum Ca(2+) store is depleted. Store-operated Ca(2+) entry has been shown to regulate B cell function but is dispensable for B cell development. By contrast, the function of IP3R-mediated Ca(2+) release in B cells remains to be determined. In this study, we generated a B cell-specific IP3R triple-knockout (IP3R-TKO) mouse model and revealed that loss of IP3Rs increased transitional B cell numbers and reduced recirculating mature B cell numbers in bone marrow. In the peripheral tissues, the numbers of conventional B2 B cells and B1 B cells were both significantly decreased in IP3R-TKO mice. Ablation of IP3Rs also dramatically reduced BCR-mediated B cell proliferation and survival. Furthermore, T cell-dependent and T cell-independent Ab responses were altered in IP3R-TKO mice. In addition, deletion of IP3Rs reduced IL-10-producing regulatory B cell numbers and led to defects in NFAT activation, which together resulted in decreased IL-10 secretion. Taken together, our study demonstrated for the first time, to our knowledge, that IP3R-mediated Ca(2+) release plays an essential role in regulating B cell development, proliferation, Ab production, and B cell regulatory function in vivo. |
