Circulating human B cells that express surrogate light chains display a unique antibody repertoire

Circulating human B cells that coexpress V-preB and conventional L chains (V-preB(+)L(+) B cells) are a recently described subset of B cells that express Abs with features of self-reactivity. Initial analysis of V-preB(+)L(+) B cells was limited to Ig-kappa and to the small, underused V(H)5 family. To determine whether Abs commonly expressed by V-preB(+)L(+) B cells show similar features, we analyzed Ig H chains from three highly expressed V-H families, V(H)1, V(H)3, and V(H)4, and Ig-lambda. We find that V(H)1 and V(H)3 Abs expressed by V-preB(+)L(+) B cells resemble V(H)5 in that they display increased J(H)6 use, long CDR3s, and an increased frequency of D-D fusions. Abs in all three of these V-H families also show skewed D reading frame use resulting in predominance of hydrophobic amino acids, which are counterselected in conventional B cells. Like Ig-kappa genes, the Ig-kappa genes in V-preB(+)L(+) B cells show long CDR3s, but they differ from Ig-kappa genes in that they display no evidence of receptor editing. We conclude that a large number of H and L chain Abs expressed by V-preB(+)L(+) B cells display features associated with self-reactive Abs.