| First Author | Takeshita H | Year | 1998 |
| Journal | Int Immunol | Volume | 10 |
| Issue | 4 | Pages | 435-44 |
| PubMed ID | 9620599 | Mgi Jnum | J:47277 |
| Mgi Id | MGI:1203251 | Doi | 10.1093/intimm/10.4.435 |
| Citation | Takeshita H, et al. (1998) Abrogation of autoimmune disease in Lyn-deficient mice by the mutation of the Btk gene. Int Immunol 10(4):435-44 |
| abstractText | Lyn and Btk play a critical role in B cell development and intracellular signaling. Lyn-deficient mice exhibit splenomegaly, elevated serum levels of IgM, production of autoantibody and glomerulonephritis with age. On the other hand, xid mice, which carry a point mutation in the btk gene, show a decrease in numbers of peripheral mature B cells, reduced serum levels of IgM and IgG3, disappearance of CD5+ B-1 cells, and low proliferative response to anti-IgM or LPS stimulation in vitro. In order to investigate the interaction between Lyn and Btk during B cell development, we established lyn-deficient xid mice. Lyn-deficient xid mice exhibited greatly reduced numbers of peripheral mature B cells, disappearance of CD5+ B-1 cells, markedly reduced serum levels of IgM and IgG3, low proliferative response to anti-IgM or lipopolysaccharide stimulation and no evidence for autoimmune disease. In addition, splenomegaly in lyn-deficient mice, which was mainly due to the accumulation of Mac-1+, cytoplasmic IgM+ lymphoblast-like cells, was also diminished in lyn- deficient xid mice. Thus, immunological abnormalities found in lyn- deficient mice were strongly affected by the absence of Btk. The present results suggest that the autoimmune symptoms in lyn-deficient mice may be caused by not only the abnormal response of B-2 cells but also that of B-1 cells, and that the interaction between Lyn and Btk is partly in tandem at the signaling pathway in B cells. |
