SURROGATE LIGHT-CHAIN EXPRESSION IS REQUIRED TO ESTABLISH IMMUNOGLOBULIN HEAVY-CHAIN ALLELIC EXCLUSION DURING EARLY B-CELL DEVELOPMENT

Allelic exclusion at the IgH locus was examined in B lineage cells of wild-type mice and mice unable to express the surrogate light chain mo lecule lambda 5 using a single-cell PCR approach. By analyzing B precu rsor cells containing two V(H)D(H)J(H) rearrangements, we found that i n wild-type animals, cells are allelically excluded as soon as mu chai ns are expressed. Furthermore, we provide evidence that in cells expre ssing D mu proteins V-H-->D(H)J(H) rearrangement is inhibited. In cont rast, in the absence of lambda 5 protein, B precursor cells were allel ically ''included,'' indicating that allelic exclusion at the IgH locu s requires expression of the pre-B cell receptor either containing a m u chain or a D mu chain. However, although mu chain double-producing B precursor cells are generated in lambda 5-deficient mice, such cells were not detected among surface immunoglobulin positive B cells.