ANATOMY OF AUTOANTIBODY PRODUCTION - DOMINANT LOCALIZATION OF ANTIBODY-PRODUCING CELLS TO T-CELL ZONES IN FAS-DEFICIENT MICE

The goal of this study was to examine the in vivo site of autoantibody production in normal and autoimmune-prone mice. B cells were identified in tissue sections with IgM- and lgG2a-specific riboprobes that readily distinguished resting cells from antibody-forming cells (AFC). In normal mice, the few identifiable lgG2a-secreting cells were found in the red pulp. By contrast, in lpr mice exceedingly high numbers of IgG2a and autoantibody-producing cells were found deep within the T cell-rich periarteriolar lymphoid sheaths (PALS). This unusual anatomic location of autoantibody-secreting B cells is unique to Fas dysregulated strains, since IgG2a-producing cells in MRL/+ and (SWR x NZB)F1 mice were found predominantly in the red pulp or outer PALS, similar to normal mice, Furthermore, analysis of spleens from lpr and non-lpr anti-DNA immunoglobulin transgenic mice revealed dramatic accumulation of Tg(+) cells in the inner PALS only in lpr mice. These data suggest that in the absence of Fas, autoreactive B cells accumulate in T cell-rich zones, and this anatomic feature may contribute to autoantibody production.