Neo-self antigens and the expansion of B-1 cells: lessons from atherosclerosis-prone mice.
The pathogenesis of atherosclerosis involves an inflammatory process that is modulated by the immune system, and within these complex responses we have discerned a possible role for an archetypic B-1 clone. We speculate that due to their immunogenicity and in vivo distribution the "neo"-self determinants created in oxidatively modified LDL are highly stimulatory for certain B-1 cell clones. These neo-self determinants, which can be created chemically, by somatic processes, may in fact represent the molecular analogues of somatic maturation, or even aging. These changes, including those on non-protein antigens induced by oxidative metabolism, amongst others, create neo-determinants against which the host no doubt can not develop rigorous B-cell tolerance. The onset of expression of these oxidative neo-determinants relatively late in development may well serve a useful function for the highly evolved mammalian immune system, as targeting by evolutionarily selected B-1 clones may facilitate the amplification of other useful antibody-mediated physiologic functions. As in the case of the T15 clone, these antibodies may aid in protection against common microbial pathogens. Hence we postulate that during the evolution of the adaptive immune system the neo-self antigenic milieu may have been exploited for the natural selection of primordial clonal specificities. The T15 B-1 clone may then illustrate a common paradigm in which there has been natural selection based on utility for the defense of the individual from environmental threats, as well as for possible "housekeeping" role(s) and the maintenance of cellular homeostasis.
Silverman
G J
GJ
Division of Rheumatology, University of California, San Diego, La Jolla, California 92093-0663, USA.
Shaw
P X
PX
Luo
L
L
Dwyer
D
D
Chang
M
M
Horkko
S
S
Palinski
W
W
Stall
A
A
Witztum
J L
JL
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis / Q000276:immunology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019070:Cell Lineage; D002999:Clone Cells / Q000276:immunology; D020022:Genetic Predisposition to Disease; D008077:Lipoproteins, LDL / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017152:Antibodies, Antiphospholipid; D001057:Apolipoproteins E; D001323:Autoantibodies; D001324:Autoantigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine