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 IgG2a-specific riboprobes that readily distinguished resting cells from antibody-forming cells (AFC). In normal mice, the few identifiable IgG2a-secreting cells were found in the red pulp. By contrast, in Ipr 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 IgG2-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 Ipr and non-Ipr anti-DNA immunoglobulin transgenic mice revealed dramatic accumulation of Tg+ cells in the inner PALS only in Ipr 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.
Jacobson
B A
BA
Department of Microbiology, Boston University School of Medicine, Massachusetts 02118, USA.
Panka
D J
DJ
Nguyen
K A
KA
Erikson
J
J
Abbas
A K
AK
Marshak-Rothstein
A
A
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D016130:Immunophenotyping; D051379:Mice; D008817:Mice, Mutant Strains; D013154:Spleen / Q000033:anatomy & histology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D019014:fas Receptor