A RECURRENT CLONOTYPE IN THE SPONTANEOUS ANTI-IGG2A RHEUMATOID-FACTORRESPONSE OF LPR LPR MICE/

We generated mice transgenic for a V-H gene that partially encodes an anti-IgG2a rheumatoid factor, Such transgenic V-H genes recombine at a low frequency with the endogenous Igh locus in mice, giving rise to a small number of B cells that express heavy chains partially encoded b y the transgene. The transgenes were crossed onto an Ipr/Ipr backgroun d, and hybridomas were generated from the resulting mice at 3 to 6 mo of age, Analysis of the anti-IgG2a-producing hybridomas obtained revea led that none expressed the transgenic V-H, Surprisingly, however, mos t of the mice yielded multiple anti-IgG2a hybridomas that expressed V, genes comprised of a single V-H gene segment, D regions with highly h omologous 5' ends encoding CDR3 regions of identical length, and the J (H)4 segment, Expressed light chain diversity among these hybridomas w as also highly restricted; most expressed a single V kappa gene segmen t, All of the hybridomas expressed members of: the V kappa 19/28 famil y, Many of the V-H genes contained a low frequency of somatic mutation , The recurrence of this family of V regions is not due to an indirect transgene effect or to effects of the genetic background used to cons truct the mice, as hybridomas expressing the predominant V gene segmen t combination were also isolated from a transgene-negative Ipr/Ipr lit termate and from MRL Ipr/Ipr mice, These data contrast with the previo us findings of others that while the spontaneous rheumatoid factor res ponse of Ipr/Ipr mice was oligoclonal, recurrent clonotypes were not a pparent, and the V-H and V kappa s encoding these rheumatoid factors c ontained a high frequency of somatic mutation whose distribution and t ype were indicative of Ag-driven selection.