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As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]

Inducibility of immunological tolerance to a T-dependent antigen, human serum albumin, was studied in autoimmune mice (NZB, MRL/Mp-1pr/1pr and male BXSB mice), comparing with non-autoimmune mice (BALB/c, DBA/2, MRL/Mp- +/+ and female BXSB mice). Weekly injections of increasing doses of the tolerogen into DBA/2 mice induced T-cell tolerance without the participation of suppressor cells and without affecting B cells. All of the autoimmune mice tested were refractory to the tolerogen; partial tolerance (40%-60% responsiveness) was attained in mice aged 1 month, but not in older mice. By comparison, tolerance was induced in non-autoimmune mice to a similar degree irrespective of the age of the mice. The tolerance inducibility was also examined in reciprocal bone marrow cell (BMC) transfer experiments between NZB and DBA/2 mice and also BMC transfer into B10.D2 mice. It was shown that recipients of NZB BMC were more resistant to tolerance induction than those of DBA/2 BMC, while irradiated NZB mice receiving DBA/2 BMC were susceptible. Hence, it is suggested that the tolerance-resistant nature of the NZB mice was inherent in T-cell precursors in the bone marrow and not in the host environment. Similar findings in support of this notion were also observed in BSXB mice. The significance of tolerance resistance in the development of autoimmunity is discussed. [ABSTRACT FROM AUTHOR]

T- and B-cell participation in the immune response induced by immune ribonucleic acid (iRNA) preparations against 1-dependent antigens was studied using athymic nude, neonatally thymectomized (NT) and cyclophosphamide-treated (CY) mice. The IRNA(T + B) preparations were made from the spleen of BALD/c mice immunized with these antigens. Injection of the IRNA into nude or NT mice caused an increase in the number of specific rosette-forming cells (RFC) and of memory cells capable of responding to secondary stimulus with a small dose of the corresponding antigen. Injection with T-dependent antigens or with iRNA(T + B) did not cause any immune response in CY mice, suggesting depletion of the if-cell function. The (RNA(T) and iRNA(B) were prepared, respectively, from the thymuses of BALD/c mice and from the spleens of nude mice which had been immunized with 1-dependent antigens. Injection of nude mice with both IRNA(T) and iRNA(S) caused an increase in the number of specific RFC and the secondary antibody formation response after boosting with a small dose of the corresponding antigen. Injection of IRNA(T) preparation into nude mice could induce the anamnestic response after boosting. However, neither of the iRNA(T) or iRNA(B) preparations could induce in nude mice the proliferation of the number of specific RFC. These results indicate the presence of at least two kinds of IRNA preparations against 1-dependent antigens and that the cooperation of IRNA(T) and IRNA(B) was required for the induction of immune response against T-dependent antigens. [ABSTRACT FROM AUTHOR]