Negative Selection at the Pre-BCR Checkpoint Elicited by Human μ Heavy Chains with Unusual CDR3 Regions

Abstract

Approximately 9% of in-frame μ heavy chain transcripts found in normal human pro-B cells encode proteins that can be expressed on the cell surface in the absence of surrogate or conventional light chains. These unusual μ heavy chains demonstrate preferential use of certain VH genes (VH3-23), frequent expression of DH regions in underrepresented reading frames, and an increased number of positively charged amino acids within the CDR3 region. Transcripts for these proteins are not found in pre-B cells or in mature B cells. When expressed in Jurkat T cells with the Igα/Igβ signal transduction module, these aberrant μ heavy chains induce cell activation and apoptosis. These results suggest that some μ heavy chains elicit negative selection at the pro-B cell to pre-B cell transition.