The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti-DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti-idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.
Article|
January 01 1990
Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.
M Shlomchik,
M Shlomchik
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
M Mascelli,
M Mascelli
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
H Shan,
H Shan
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
M Z Radic,
M Z Radic
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
D Pisetsky,
D Pisetsky
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
A Marshak-Rothstein,
A Marshak-Rothstein
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
M Weigert
M Weigert
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
M Shlomchik
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
M Mascelli
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
H Shan
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
M Z Radic
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
D Pisetsky
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
A Marshak-Rothstein
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
M Weigert
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 171 (1): 265–292.
Citation
M Shlomchik, M Mascelli, H Shan, M Z Radic, D Pisetsky, A Marshak-Rothstein, M Weigert; Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.. J Exp Med 1 January 1990; 171 (1): 265–292. doi: https://doi.org/10.1084/jem.171.1.265
Download citation file: