| First Author | Samardzic T | Year | 2002 |
| Journal | Eur J Immunol | Volume | 32 |
| Issue | 9 | Pages | 2481-9 |
| PubMed ID | 12207332 | Mgi Jnum | J:78999 |
| Mgi Id | MGI:2386808 | Doi | 10.1002/1521-4141(200209)32:9<2481::AID-IMMU2481>3.0.CO;2-C |
| Citation | Samardzic T, et al. (2002) CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice. Eur J Immunol 32(9):2481-9 |
| abstractText | BOB.1/OBF.1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is knownas a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF.1-deficient mice might be due to CD22 up-regulation. Mice weregenerated lacking both genes. In BOB.1/OBF.1xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca(2+) mobilization. This Ca(2+)-signalling defect was restored in BOB.1/OBF.1xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF.1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism. |
