Immune Responses in Vitro

Newbonr mice were treated from the day of birth with either bovine gamma globulin or anti-mu chain sera. The latter was administered using a protocol known to produce suppression of gammaM, gammaG, and gammaA production. Subsequent immunization with ovalbumin (OA) in alum was attempted to see if suppression of gammaM, gammaG, and gammaA classes of antibody would also be accompanied by suppression of gammaE-producing capacity. gammaG and gammaM antibody to OA and mercaptoethanol-resistant (gammaG) antibody to OA were measured by passive hemagglutination; gammaG and gammaE anti-OA antibodies were measured by passive cutaneous anaphylaxis. Anti-mu suppression was achieved with significant reduction in gammaM and gammaG antibodies. gammaE antibodies were not affected, suggesting an ontogenetic development for gammaE-bearing lymphocytes independent of the previously described gammaM to gammaG to gammaA ontogenetic sequence.

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

The effect of anti-mu suppression of gammaM and gammaG on the production of gammaE.

Dwyer

Rosenbaum

Lewis

1976

“…It is not yet clear, however, whether IgM and IgG producers have separate precursors as opposed to a single precursor capable to switching from IgM to IgG (30,31,(35)(36)(37)(38)(39). Our observation that nonimmunized mice contain exclusively ABC with IgM receptors cannot be interpreted in favor of the latter hypothesis, because there might be separate precursors, all of which have IgM receptors, with some of them differentiating into IgM producers and others into IgG producers.…”

Section: Discussioncontrasting

confidence: 46%

Genetic Control of the Immune Response

Hämmerling

Masuda

McDevitt

1973

The influence of immunization with (T,G)-A--L on the frequency and characteristics of [125I] (T,G)-A--L-binding cells (ABC) was investigated in high and low responder mice, whose ability to respond to (T,G)-A--L is under control of an H-2-linked immune response gene, Ir-1. Unimmunized high and low responder mice have about the same number of ABC in spleen and lymph nodes (6–12 ABC/104). However, after immunization with (T,G)-A--L in aqueous solution, ABC in high responders increase to a much greater extent than they do in low responders. By inhibition of ABC with class-specific anti-Ig sera, it was demonstrated that in nonimmune and primed mice antigen is bound to IgM receptors, which is in agreement with the exclusive production of 19S anti-(T,G)-A--L antibody in primed animals. In contrast, after secondary challenge with antigen, ABC in high and low responder mice have mainly IgG receptors, although under the conditions used for immunization, low responders are not able to produce detectable amounts of 7S anti-(T,G)-A--L antibody. From these results and from the evidence that low responders very probably have a T cell defect, it is suggested that the switchover from IgM to IgG precursor cells can be induced by antigen itself, without the action of specific T cells. Furthermore, the failure of marked proliferation of ABC in low responders after antigenic stimulation is explained by the lack of stimulation by specific T cells. By independent methods it has been shown that all ABC detected in this study are B cells. Preliminary experiments indicate that purified peripheral T cells bind antigen, but much less per cell than do B cells.

“…Accumulating evidence claims that B cells having/~-chain determinants on their surface are the precursors of both IgM and IgG forming cells (25,26). Such virgin B cells, termed B/z cells, would differentiate either directly into IgM-forming cells or into the cells having both /~-and ~/-chains on their surface (B/~' cells) that consequently become B~' cells, the precursors of IgG forming cells (27,28).…”

Section: Discussionmentioning

confidence: 99%

Selective Roles of Thymus-Derived Lymphocytes in the Antibody Response

Tada

Takemori

1974

It is rapidly becoming clear that in certain antibody responses thymus-derived lymphocytes (T cells) are definitely endowed with a role to suppress responses of bone marrow-derived lymphocytes (B cells) to antigen (1-12). Such inhibitory effect of T cells led to a designation of "suppressor T cell" and is being recognized in large measure as an important regulatory device in various antibody responses. Some forms of immunological tolerance are also explained by the active suppression by T cells rather than the elimination of B-cell clones (12)(13)(14).The suppression by T cells has been shown to be mediated by both antigenspecific and nonspeclfiC mechanisms, while both pathways may be equally important for the regulation of antibody synthesis. Our previous studies (3) demonstrated that T cells primed with a carrier antigen suppressed an ongoing IgE antibody synthesis by B cells against a hapten coupled to the same carrier; thus this suppression appeared to be antigen-specific. The presence of a subcellular component of T cells that specifically suppresses the B-cell response was also reported (15).Our more recent studies on the specific suppression of IgM antibody response by T cells (11) showed another important fact, namely, that the T cell's suppressive effect on B cells varied depending on the time when the suppressor cells were given to the immunized recipients. The suppressor effect on the IgM antibody response was found to be more pronounced if the primed T cells were given to the recipients at a time when antibody-forming cells were starting to appear in their spleen rather than at the time of immunization. These observations suggest that the susceptibility of B cells to the suppressive effect of T cells is inherently different depending on the maturation stage of B cells and on the immunoglobulin classes which they are destined to produce. The present experiments were undertaken to study the mode and sites of action of suppressor T cells on antibody response in mice with special reference to the differential effect of T cells on B cells which produce IgM and IgG antibodies.