Role of Bruton's tyrosine kinase in B cell development.
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 in vivo. 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, resulting 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.
Maas
A
A
Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.
Hendriks
R W
RW
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D002454:Cell Differentiation; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014960:X Chromosome
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse