T cell dependence of the "natural" autoreactive B cell activation in the spleen of normal mice.
A high frequency of clonal precursor B cells producing lytic antibodies to syngeneic erythrocytes treated with bromelain (BMRC) is revealed in normal mouse spleen cells by lipopolysaccharide-driven limiting dilution analysis. All such specificities are recovered as activated blasts after density gradient fractionation, the "small lymphocyte" pool being depleted of anti-BMRC reactivities. In contrast, the spleens of athymic (nude) mice contain undetectably low frequencies of these specificities in either lymphocyte compartment. Transfer of relatively low numbers of normal syngeneic splenic T lymphocytes to adult nude mice restores the high frequency of anti-BMRC clonal precursor B cells, again in the activated, but not in the resting spleen cell fractions. Large total T cells are more than tenfold better than resting T cells in reconstitution potential, as are enriched CD4+ as compared to CD8+ cells which are practically devoid of activity in this respect. These results apply exclusively to B cells at a differentiative stage that allows for extensive clonal expansion, since there is a marked difference between the frequency of clonal precursors determined by limiting dilution analysis and the frequency of Ig-secreting plaque-forming cells of the same specificity, and induced by the same mitogen in short-term cultures. The implications of these findings for the physiology of autoreactivity and repertoire selection in the compartment of perinatal B cells are discussed.
Huetz
F
F
Laboratory of Immunobiology, Pasteur Institute, Paris, France.
Sciard-Larsson
E L
EL
Pereira
P
P
Portnoi
D
D
Coutinho
A
A
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D001963:Bromelains; D002999:Clone Cells / Q000276:immunology; D004912:Erythrocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D008070:Lipopolysaccharides; D001963:Bromelains