Ig-alpha cytoplasmic truncation renders immature B cells more sensitive toantigen contact

To study the function of Ig-alpha in the selection of autoreactive B cells, we have analyzed mb-1 cytoplasmic truncation mutant mice (mb-1(Delta c/Del ta c)), which coexpress transgenes encoding hen egg lysozyme (HEL) and HEL- specific immunoglobulin. We demonstrate that in the presence of soluble MEL (sHEL) and dependent on the mb-1(Delta c) mutation, most immature B cells bearing the MEL-specific Ig transgene undergo rearrangements of endogenous kappa light chains, resulting in loss of MEL specificity. Moreover, immatur e B cells from Ig-alpha mutant mice respond to BCR cross-linking with an ex aggerated and prolonged calcium response and induction of protein tyrosine phosphorylation. Our data imply a negative signaling role for Ig-alpha in i mmature B cells.