Spontaneous increase of plasma-like cells with high GANP expression in the extrafollicular region of lymphoid organs of autoimmune-prone mice

Autoimmune-prone mice bear a hyper-active B cell population generated spontaneously in peripheral lymphoid organs. Expression of β RNA-primase GANP was shown to be an activation marker in lymphoid follicle germinal center (GC) B cells after immunization with T cell-dependent antigen (TD-Ag) in normal mice. In this study, we examined the expression of GANP in lymphoid tissues of autoimmune-prone mice. GANP expression was up-regulated in GC-B cells after stimulation with TD-Ags; however, highly GANP-positive (GANP^hi) cells were also observed in lymph nodes of non-immunized MRL/lpr mice. GANP^hicells in lymph nodes as well as in spleens of the different autoimmune-prone strains, MRL/lpr, NZB, (NZB×NZW)F1 and BXSB, gradually increased with age. This population was detected only in small numbers in the red pulp region of the spleen after immunization with TD-Ag in normal C57BL/6 and BALB/c mice. GANP^hicells had a B220^-IgM⁺Syndecan-1⁺phenotype, but were negative for PAS-staining and bromo-deoxyuridine incorporation. These results demonstrate that GANP^hiplasma-like cells appear in lymph nodes of autoimmune mice during aging, suggesting that the new plasma cell population might be generated after hyper-activation of B cells during the course of autoimmune disease.