Autoimmune-prone mice bear a hyper-active B cell population generated spontaneously in peripheral lymphoid organs. Expression of beta 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/1pr mice. GANP(hi) cells in lymph nodes as well as in spleens of the different autoimmune-prone strains, MRL/1pr, NZB, (NZB x 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(hi) cells had a B220(-)IgM(+)Syndecan-1(+) phenotype, but were negative for PAS-staining and bromo-deoxyuridine incorporation. These results demonstrate that GANP(hi) plasma-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. (C) 2003 Elsevier Science Ltd. All rights reserved.