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Critical Reviews™ in Immunology

Impact factor: 3.857

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v16.i3.20
pages 251-274

Structural Aspects of Signal Transduction in B-Cells

Mauno Vihinen
Department of Biosciences, Division of Biochemistry, P.O. Box 56, FIN-00014 University of Helsinki, Finland
C. I. Edward Smith
Center for BioTechnology, Karolinska Institute, Department of Bioscience at NOVUM. S-14157 Huddinge, Sweden, and Department of Clinical Immunology, Karolinska Institute at Huddinge Hospital, S-14186 Huddinge, Sweden

ABSTRACT

Signal transduction in hematopoietic cells is a highly specific process. The stimulation of B cell receptor following antigen binding triggers, as a first step, phosphorylation of the cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs). Src family tyrosine kinases Blk, Fyn, Lck, and Lyn as well as spleen kinase, Syk, are activated to transmit the signal further. In this review the signaling events are discussed in structural terms. The factors related to B cell maturation and their targeted mutations are reviewed. During the last 2 years plenty of structural information concerning signaling molecules in B cells has been obtained by using X-ray crystallography, NMR spectroscopy, molecular modeling, and mutational analysis. The molecules discussed include Src family kinases, Syk, Grb2 adaptor protein, and Tec family kinases Bmx and Btk. The structure, function, and interactions of these signaling compounds are described in atomic detail.