Genetic diversity of murine rheumatoid factors.
Anti-Ig autoantibodies (rheumatoid factors, RF) have been implicated in the pathogenesis of human and murine rheumatoid arthritis as well as in the regulation of normal immune responses. Their genetic origin, clonal diversity, and inducing agents, and the relatedness between RF associated with disease and those occurring under physiologic conditions are not well understood. In this study, the genetic and clonotypic origin of 34 monoclonal IgM RF-secreting hybridomas from arthritic MRL-lpr/lpr and nonarthritic MRL-+/+ and C57BL/6-lpr/lpr mice was examined by RNA hybridization. For this purpose, we used probes for 10 VH and 13 Vk gene families as well as all JH and Jk gene segments. The majority of hybridomas expressed distinct Ig gene segment patterns and, hence, were clonally unrelated. Overall, a variety of different V and J gene segments were expressed in the hybridoma panel, suggesting that a large number of distinct genetic elements participates in expression of RF-like activity. RF from arthritic mice expressed Vk messages from the overlapping Vk22 and Vk28 gene families more frequently than did those from nonarthritic mice. RF from autoimmune MRL mice, both arthritic MRL-lpr/lpr and nonarthritic MRL-+/+, showed skewed JH4 segment usage, whereas those from C57BL/6-lpr/lpr preferentially expressed JH2.
Duchosal
M A
MA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Kofler
R
R
Balderas
R S
RS
Aguado
M T
MT
Dixon
F J
FJ
Theofilopoulos
A N
AN
D000818:Animals; D000916:Antibody Diversity; D000918:Antibody Specificity; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000378:metabolism; D007074:Immunoglobulin G / Q000145:classification / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D012217:Rheumatoid Factor / Q000096:biosynthesis / Q000235:genetics*
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012217:Rheumatoid Factor