International Immunology, Vol. 13, No. 4, 485-493,
April 2001
© 2001 Japanese Society for Immunology
Bruton's tyrosine kinase is required for signaling the CD79b-mediated pro-B to pre-B cell transition
1 Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan
2 Department of Immunology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome Bunkyo-ku, Tokyo 113-8613, Japan
3 Howard Hughes Medical Institute, and Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 675 Circle Drive South, Los Angeles, CA 90095, USA
Correspondence to: K. Takatsu
Formation of the pre-BCR complex is a critical check point during B cell development and induces the transition of pro-B to pre-B cells. CD79b (Igß) is a signaling component in the pre-BCR complex, since differentiation to the pre-B phenotype is induced by cross-linking the CD79b expressed on developmentally arrested pro-B cells from recombination-activating gene (RAG)-2-deficient mice. Bruton's tyrosine kinase (BTK) plays important roles in B cell development. However, its molecular mechanisms in early B cell development are not fully understood. To examine whether BTK functions in CD79b-mediated signaling for the pro-B/pre-B transition, we utilized RAG2/BTK double-knockout (DKO) mice. Pro-B cells from RAG2/BTK-DKO mice did not differentiate into pre-B cells following CD79b cross-linking, although tyrosine phosphorylation of cellular proteins including Erk1/2 and phospholipase C-
2 was induced in the same manner as RAG2-KO mice. BTK is phosphorylated after cross-linking of CD79b on RAG2-deficient pro-B cells. These findings suggest that BTK-dependent pathways downstream of CD79b are critical for the pro-B/pre-B transition and BTK-independent signaling pathways are also activated via the pre-BCR complex.
Keywords: B cell development, Bruton's tyrosine kinase-deficient mice, Igß, pre-BCR, recombination-activating gene-2-deficient mice
4 Present address: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation,825 North East 13th Street, Oklahoma City, OK 73104, USA
Transmitting editor: T. Watanabe
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