MacKenzie, Lorna Elizabeth; (1992) Characterisation of human CD5 B cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The human 67kDa glycoprotein termed CD5, is equivalent to Ly1 (B-1) in the mouse. This molecule was, originally, described as a pan-T cell marker. Evidence has been accumulating, suggesting that the B cells carrying this marker, would play a key role as producers of antibodies to self-constituents. These studies were initiated, to clarify the repertoires of human CD5 B cells. CD5 molecules were found to be barely detectable on a minority of circulating B lymphocytes. A number of techniques improved the sensitivity of their detection and it was established that the blood of some patients with autoimmune disease, may, in fact, have a higher number of this subpopulation of B cells. Furthermore, chronic lymphocytic leukemia B cells, expressing CD5, were shown to produce auto and polyreactive antibodies. Since it was found that a high proportion of B cells, early in development, express CD5, clones were established by Epstein-Barr virus transformation of CD5+ and CD5- cord blood B lymphocytes, separated by flow cytometry. IgM from many of both CD5+ and CD5- clones reacted with a variety of autoantigens. Examination for expression of cross-reactive idiotypes, associated with defined VH and VK subgroups, revealed that auto and polyreactivity does not appear to be the property of any particular V gene family. Indeed, IgM produced by both subsets of cord blood B cells, were found with equal frequencies of expression of VhI and VhIH associated idiotopes. In contrast, a higher frequency of a VKllIb subgroup associated idiotope, the phenotypic marker for the VK32S germline gene, was found in the CD5+ clones and of particular interest was the restricted association of the CD5 B cells with a VHIV subfamily. In conclusion, differences may exist in the expression of certain germline genes between CD5+ and CD5- cord blood B cells and may indicate an expansion of CD5 B cells within the fetal environment.

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