| First Author | Kersseboom R | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 9 | Pages | 2643-54 |
| PubMed ID | 20623551 | Mgi Jnum | J:165753 |
| Mgi Id | MGI:4838383 | Doi | 10.1002/eji.201040521 |
| Citation | Kersseboom R, et al. (2010) Constitutive activation of Bruton's tyrosine kinase induces the formation of autoreactive IgM plasma cells. Eur J Immunol 40(9):2643-54 |
| abstractText | B-cell receptor (BCR)-mediated signals provide the basis for B-cell differentiation in the BM and subsequently into follicular, marginal zone, or B-1 B-cell subsets. We have previously shown that B-cell-specific expression of the constitutive active E41K mutant of the BCR-associated molecule Bruton's tyrosine kinase (Btk) leads to an almost complete deletion of immature B cells in the BM. Here, we report that low-level expression of the E41K or E41K-Y223F Btk mutants was associated with reduced follicular B-cell numbers and significantly increased proportions of B-1 cells in the spleen. Crosses with 3-83 mu delta and VH81X BCR Tg mice showed that constitutive active Btk expression did not change follicular, marginal zone, or B-1 B-cell fate choice, but resulted in selective expansion or survival of B-1 cells. Residual B cells were hyperresponsive and manifested sustained Ca(2+) mobilization. They were spontaneously driven into germinal center-independent plasma cell differentiation, as evidenced by increased numbers of IgM(+) plasma cells in spleen and BM and significantly elevated serum IgM. Because anti-nucleosome autoantibodies and glomerular IgM deposition were present, we conclude that constitutive Btk activation causes defective B-cell tolerance, emphasizing that Btk signals are essential for appropriate regulation of B-cell activation. |
