| First Author | Xu S | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 8 | Pages | 4690-8 |
| PubMed ID | 16585562 | Mgi Jnum | J:131161 |
| Mgi Id | MGI:3773096 | Doi | 10.4049/jimmunol.176.8.4690 |
| Citation | Xu S, et al. (2006) Phospholipase Cgamma2 dosage is critical for B cell development in the absence of adaptor protein BLNK. J Immunol 176(8):4690-8 |
| abstractText | B cell linker (BLNK) protein and phospholipase Cgamma2 (PLCgamma2) are components of the BCR signalosome that activate calcium signaling in B cells. Mice lacking either molecule have a severe but incomplete block in B lymphopoiesis. In this study, we generated BLNK-/- PLCgamma2-/- mice to examine the effect of simultaneous disruption of both molecules on B cell development. We showed that BLNK-/- PLCgamma2-/- mice had compounded defects in B cell maturation compared with either single mutant, suggesting that these two molecules cooperatively or synergistically signaled B lymphopoiesis. However, Ig H chain allelic exclusion was maintained in single and double mutants, indicating that signals propagated by BLNK and PLCgamma2 were not involved in this process. Interestingly, in the absence of BLNK, B cell development was dependent on plcgamma2 gene dosage. This was evidenced by the proportionate decrease in splenic B cell population and increase in bone marrow surface pre-BCR+ cells in PLCgamma2-diploid, -haploid, and -null animals. Intracellular calcium signaling and ERK activation in response to BCR engagement were also proportionately decreased and delayed, respectively, with stepwise reduction of plcgamma2 dosage in a BLNK(null) background. Thus, these data indicate the importance of BLNK not only as a conduit to specifically channel BCR-signaling pathways and as a scaffold for the assembling of macromolecular complex, but also as an efficient aggregator or concentrator of PLCgamma2 molecules to effect optimal signaling for B cell generation and activation. |
