J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/05/1753/06 $2.00
Volume 185, Number 10, May 19, 1997 1753-1758

The Immunoglobulin (Ig) and Ig Cytoplasmic Domains Are Independently Sufficient to Signal B Cell Maturation and Activation in Transgenic Mice

By Yih-Miin Teh, and Michael S. Neuberger

From the Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

The B cell antigen receptor, composed of membrane immunoglobulin (Ig) sheathed by the Ig/Ig heterodimer plays a critical role in mediating B cell development and responses to antigen. The cytoplasmic tails of Ig and Ig differ substantially but have been well conserved in evolution. Transfection experiments have revealed that, while these tails share an esssential tyrosine-based activation motif (ITAM), they perform differently in some but not all assays and have been proposed to recruit distinct downstream effectors. We have created transgenic mouse lines expressing chimeric receptors comprising an IgM fused to the cytoplasmic domain of each of the sheath polypeptides. IgM/ and IgM/ chimeras (but not an IgM/ with mutant ITAM) are each independently sufficient to mediate allelic exclusion, rescue B cell development in gene-targeted Igµ mice that lack endogenous antigen receptors, as well as signal for B7 upregulation. While the (IgM/) × (IgM/) double-transgenic mouse revealed somewhat more efficient allelic exclusion, our data indicate that each of the sheath polypeptides is sufficient to mediate many of the essential functions of the B cell antigen receptor, even if the combination gives optimal activity.

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