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Developmental Immunology
Volume 8, Issue 3-4, Pages 171-181
http://dx.doi.org/10.1155/2001/28962

Role of Bruton's Tyrosine Kinase in B Cell Development

1Department of Cell Biology and Genetics, Erasmus University Rotterdam, PO Box 1738, Rotterdam 3000 DR, The Netherlands
2Department of Immunology, Erasmus University Rotterdam, PO Box 1738, Rotterdam 3000 DR, The Netherlands

Copyright © 2001 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

X-linked agammaglobulinemia (XLA) is one of the most frequent inherited immunodeficiency diseases in man and is characterized by an almost complete arrest of B cell differentiation at the pre-B cell stage. The gene defective in XLA encodes the cytoplasmic signaling molecule Bruton's tyrosine kinase (Btk). Next to the CBA/N strain of mice, carrying a single amino acid substitution mutation in the Btk gene, which results in the X-linked immunodeficiency (xid) phenotype, additional mouse models have been developed to study the role of Btk invivo. This review discusses the analyses of Btk null-mutants, obtained by gene targeting in embryonic stem cells, and transgenic mice that express wild-type or mutated forms of the Btk gene. These studies provided information on the function of Btk at several important checkpoints throughout B cell development. Analyses of the mouse models indicated that Btk is not essential for pre-B cell receptor signaling in the mouse. By contrast, Btk-mediated B cell receptor signaling appears to be required for the survival of immature B cells in the bone marrow, that have performed a successful immunoglobulin (Ig) L chain locus rearrangement, resultirig in the expression of a non-autoreactive Ig on the membrane. Btk is also shown to be involved in signaling pathways that govern the development of peripheral B cells, including follicular entry, follicular maturation and plasma cell differentiation.