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Circulating Human B Cells That Express Surrogate Light Chains Display a Unique Antibody Repertoire¹

Eric Meffre^*,, Michael Chiorazzi^* and Michel C. Nussenzweig^2,*,

^* Laboratory of Molecular Immunology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021

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- and to the small, underused V_H5 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_H1, V_H3, and V_H4, and Ig-. We find that V_H1 and V_H3 Abs expressed by V-preB⁺L⁺ B cells resemble V_H5 in that they display increased J_H6 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- genes, the Ig- genes in V-preB⁺L⁺ B cells show long CDR3s, but they differ from Ig- 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.

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