HUMAN THYMIC B-CELLS LARGELY OVEREXPRESS THE V(H)4 IG GENE FAMILY - APOSSIBLE ROLE IN THE CONTROL OF TOLERANCE IN-SITU

Human thymus contains a small population of B cells, a fraction of whi ch expresses CD2 and/or CD5, as revealed by FACS analysis. Human thymi c B cells enriched on CD19 panning revealed a constant co-expression o f CD19 and Ig light chains. In the absence of detectable a precursors these cells had reached at least the stage of IgM(+) immature B lympho cytes. Analysis of Ig transcripts by PCR amplification first revealed a strong bias in favor of the V(H)4 and sequencing of 45 V(H)4-D-J cDN A clones isolated from two thymuses indicated that this thymic reperto ire significantly differed from that of peripheral blood lymphocytes. Most genes of the V(H)4 family were used with various DJ combinations and a relatively high frequency of somatic mutations. This repertoire thus appears clearly selected in the thymus. This is of particular int erest since the V(H)4 gene family is frequently encountered in autoimm unity, a situation in which the number of thymic B cells is largely in creased. They could play a major role in the control of tolerance in s itu.