IGG(-LEUKEMIA B-CELLS - PRODUCTION OF IGG ANTIBODIES THAT EXHIBIT DIMINISHED AUTOREACTIVITY AND IGG SUBCLASS SKEWING(), CD5(+) HUMAN CHRONIC LYMPHOCYTIC)

Several questions exist regarding CD5(+) B cells. These include the ab ility of these cells, as compared to CD5(-) B cells, to undergo an Ig isotype class switch, the subclasses utilized, and the effects that sw itching may have on antigen binding. To address these issues, ten pati ents with chronic lymphocytic leukemia (CLL) whose CD5(+) leukemic B c ell clones produced IgG were studied. Monoclonal IgG was collected fro m PMA-stimulated CLL cells and from heterohybridomas constructed with these cells, and then analyzed for IgG subclass utilization, autoreact ivity, and DNA idiotype expression. The monoclonal B cells from 80% of the CLL patients produced IgG I and those from 20% produced IgG3. Non e produced IgG2. In contrast to the known autoreactivity of IgM-produc ing CD5(+) CLL cells (> 50% autoreactive), none of these IgG antibodie s reacted significantly with the autoantigens tested. However, three d id react significantly with autoantigen after artificially increasing antibody valency by crosslinking. Whereas five of the IgG molecules ex pressed a cross reactive idiotypic (CRI) marker characteristic of non- mutated kappa anti-DNA antibodies, three expressed a CRI displayed pri marily on mutated IgG anti-DNA antibodies. Thus, some CD5(+) human B c ells can undergo an isotype class switch that for these CLL cells is b iased against IgG2 and in favor of the IgG1 and IgG3. In their native state the IgG molecules secreted by these isotype-switched CD5 cells h ave diminished autoreactivity, as compared to IgM-producing CLL cells. Since some of the IBG antibodies could be made auto- and poly-reactiv e by increasing antigen-binding valency, while others expressed idioty pic markers of mutated antibodies, certain of these CD5(+) B cells pro bably utilize non-mutated Ig V genes coding for polyreactive antibodie s, whereas others may use genes that have undergone somatic mutation a nd that code for more restricted specificities. Therefore, both valenc y and V-H gene mutation may account for the diminished autoreactivity of these CD5(+) B cell-derived IgG antibodies.