Volume 271, Number 39, Issue of September 27, 1996 pp. 23786-23791
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Regulation of ITAM Signaling by Specific Sequences in Ig- B Cell Antigen Receptor Subunit

(Received for publication, May 3, 1996)

Sylvanie Cassard , Daniel Choquet , Wolf Herman Fridman and Christian Bonnerot

From  CJF 95-01, INSERM, Institut Curie, 75231 Paris cedex 05,  Unité 261, INSERM, Institut Pasteur, Paris, and  Unité 255, INSERM, Institut Curie, 75231 Paris cedex 05, France

B cell antigen receptors (BCR) are composed of an antigen binding subunit, the membrane Ig, and Ig-/Ig- heterodimers, that contain a transducing motif named ITAM for ``immuno-receptor tyrosine-based activation motif.'' Ig- and Ig- ITAMs only differ by four amino acids located before the second conserved tyrosine (DCSM in Ig- and QTAT in Ig-), which determine the in vitro association of Ig- with the src kinase fyn. We have previously shown that Ig- and Ig- BCR subunits activate different signaling pathways by expressing, in B cells, FcRII chimeras containing the cytoplasmic tails of Ig- or Ig-. We report here that the signaling capacity of Ig- ITAM is regulated by peptide sequences located inside (QTAT region) or outside the ITAM (flanking sequences). Furthermore, when isolated, Ig- and Ig- ITAM have similar abilities as the entire Ig- tail and the whole BCR in triggering tyrosine kinase activation, an increase of intracellular calcium concentration as well as late events of cell activation as assessed by cytokine secretion. These data show that alterations that modify the ability of Ig- and Ig- to interact in vitro with the src kinase fyn (switch between QTAT and DCSM) also determine signal transduction capabilities of these molecules expressed in B cells.

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