Cross-reactivity of IgG and IgM secreting B cells in normal and autoimmune mice

Antibodies from animals with lupus react with a diverse array of foreign and self antigens. This has been attributed to the activation of large numbers of mono-specific B cells, although it could result from the stimulation of a smaller population of highly cross-reactive lymphocytes. To examine this issue, a chamber ELIspot assay was used to compare the cross-reactivity of Ig-secreting B cells from autoimmune vs normal mice. The cross-reactivity of IgM-secreting lymphocytes was significantly greater than that of IgG-secreting cells in normal BALB/c and DBA/2 mice. For example, 5-23% of IgM but only 0.1%-0.4% of cells secreting IgG antibodies against DNA or TNP-BSA were cross-reactive. When normal animals were immunized and boosted with TNP-KLH, the resultant IgG anti-TNP response was essentially mono-specific. There was no significant difference in the proportion of lymphocytes producing cross-reactive IgM antibodies in normal vs autoimmune mice. In contrast, the frequency of cross-reactive IgG-secreting B cells in lupus-prone MRL-lpr/lpr and (NZB x NZW)F1 animals was at least 15 times higher than in normal mice. These observations indicate that the repertoire of IgG-secreting cells in active lupus differs qualitatively from that seen spontaneously or following antigenic stimulation in normal animals.