Human thymic B cells largely overexpress the VH4 Ig gene family. A possible role in the control of tolerance in situ?

Human thymus contains a small population of B cells, a fraction of which expresses CD2 and/or CD5, as revealed by FACS analysis. Human thymic B cells enriched on CD19 panning revealed a constant co-expression of CD19 and Ig light chains. In the absence of detectable B precursors, these cells had reached at least the stage of IgM+ immature B lymphocytes. Analysis of Ig transcripts by PCR amplification first revealed a strong bias in favor of the VH4 and sequencing of 45 VH4-D-J cDNA clones isolated from two thymuses indicated that this thymic repertoire significantly differed from that of peripheral blood lymphocytes. Most genes of the VH4 family were used with various D-J combinations and a relatively high frequency of somatic mutations. This repertoire thus appears clearly selected in the thymus. This is of particular interest since the VH4 gene family is frequently encountered in autoimmunity a situation in which the number of thymic B cells is largely increased. They could play a major role in the control of tolerance in situ.