title: Dissociation of severe lupus-like disease from polyclonal B cell activation and IL 2 deficiency in C3H-lpr/lpr mice.
abstract: The lymphoproliferation characteristic of all strains of mice homozygous for the gene lpr results from the expansion of an unusual subset of cells that express reduced levels of Ly-1 and Thy-1 antigens and high levels of Ly-5(B220), an antigen that is normally only detected on cells of the B lineage. In the present study, C3H-lpr mice were studied to determine when this population of cells first appears in lymph node (LN) and spleen and whether its appearance relates to the development of B cell activation and deficiencies in interleukin 2 (IL 2) production. The results showed that Ly-5(B220)+, sIg- cells were first detected in LN at 4 wk of age; thereafter their numbers increased exponentially until at 16 wk of age they represented more than 80% of LN cells. Two subpopulations of Ly-5(B220)+, sIg- cells were present in LN; one Ly-1+, Thy-1+ and the other Ly-1+, Thy-1-. Ly-5(B220)+, sIg- cells were not detected in C3H-lpr spleen until 6 to 10 wks after their appearance in LN, and their proportions never reached those in LN. Polyclonal B cell activation in C3H-lpr spleens was not observed until Ly-5(B220)+, sIg- cells were present, suggesting that this population may play a role in B cell stimulation. IL 2 production by C3H-lpr spleen and LN cells was normal up to 6 wk of age and was significantly impaired thereafter, with LN being more severely affected than spleen. The IL 2 defect could be significantly repaired by the addition of PMA to the cultures. Although defective IL 2 production coincided with the appearance of Ly-5(B220)+, sIg- cells in LN, it preceded the appearance of these cells in spleen. In spite of the impaired ability to produce IL 2 in vitro, CTL responses to alloantigens were normal. Although C3H-lpr mice share many of the lymphoid abnormalities observed in MRL-lpr mice, they do not develop severe, early-onset SLE-like disease characteristic of the latter strain. This suggests that factors other than defective IL 2 production and polyclonal B cell activation are required for the development of fulminant autoimmune disease.
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008215:Lymphocytes, Null / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell