Antibody response of mice following neonatal treatment with a monoclonal anti‐receptor antibody. Evidence for B cell tolerance and T suppressor cells specific for different idiotopic determinants

Černý, Jan; Cronkhite, R; Heusser, Christoph

doi:10.1002/eji.1830130313

Cited by 19 publications

(17 citation statements)

References 30 publications

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“…Previous studies from this and other laboratories (11,21,24,25) have demontrated that responses of the T 15 idiotype can be markedly suppressed when BALB/c mice are treated as neonates with large amounts of anti-T15 antibody. Recent studies from other laboratories (21) have demonstrated that this suppression can be obtained by treatment of neonatal mice with the AB1-2 monoclonal antibody.…”

Section: Response To Pc Of Cells Derived From Mice That Were Neonatalmentioning

confidence: 81%

“…After removal of sIg + cells from the bone marrow population, the frequency of remaining cells responsive to PC was ~ 1/ 20 million injected cells, or 8.8% of the frequency of spleen cells. Since <2% of (11,21). One of these, AB1-2, has proven extremely useful in standardizing assays for indicating the presence of markers that are diagnostic of members of the T 15 family.…”

Section: Resultsmentioning

confidence: 99%

“…Often such clonotypes dominate the in vivo and in vitro response to given antigens. The response to phosphorylcholine (PC) ~ of BALB/c mice is one such response, wherein the repertoire of responsive clonotypes includes over 100 distinct specificities (10,11), yet one clonotype, that which is indistinguishable from the TEPC-15 (T 15) myeloma protein, represents the majority of the response (5)(6)(7)(8)(9)(10)(11). The basis for such clonai dominance within an immune response is not yet fully understood.…”

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confidence: 99%

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Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Stone¹

1983

The Journal of Experimental Medicine

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To evaluate the role of environmental selective processes, as opposed to variable region gene expression, in the determination of B cell repertoire expression, we have assessed the phosphorylcholine (PC)-specific repertoire of precursor cells that remain in bone marrow cell populations after the removal of surface immunoglobulin (sIg)-bearing cells. Such cells are assumed to represent a stage in B cell maturation before the expression of sIg, and thus at a time when they have not as yet interfaced with environmental influences that operate through sIg receptors such as antigenic stimulation, tolerance, or antiidiotypic regulation. The repertoire as expressed in these cells, therefore, should reflect the readout of immunoglobulin variable region genes as they are expressed in progenitors to B cells. The results of these studies indicate that, as in mature primary B cell pools of BALB/c mice, the majority of PC-responsive sIg- bone marrow cells are of the T15 clonotype. Thus, environmental selective mechanisms would not appear to be required for the high frequency of B cells of the T15 idiotype in the primary B cell repertoire of BALB/c mice. Analysis of the sIg- bone marrow cells in (CBA/N X BALB/c)F1 male mice demonstrated that the deficit of PC-responsive mature B cells, which is a characteristic of this murine strain, must occur after receptor expression, since a normal frequency of PC-responsive and T15-expressing cells is present in their sIg- bone marrow population. Finally, these same mice were used to obtain bone marrow cell preparations from individual leg bones, so as to permit an analysis of the occurrence of T15+ and T15- clonotypes within individual bone marrow populations. The findings from these studies indicate that T15+ B cells occur as a high frequency event within bone marrow generative cell pools. Furthermore, bone marrow populations that are positive for PC-responsive precursor cells often display multiple copies of such precursor cells that are exclusively either T15+ or T15-. This finding indicates that clonal expansion of cells within the B cell lineage apparently occurs before immunoglobulin receptor acquisition.

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Section: Response To Pc Of Cells Derived From Mice That Were Neonatalmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Stone¹

1983

The Journal of Experimental Medicine

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“…The only exposure of pups in the second generation to the E. coli antigen had been through the immune network of the mother. Although the mechanism for this shaping of the immune network is not yet fully understood, it is known that neonatal treatment with monoclonal antibody can cause selection and expansion of both the B-cell and T-cell repertoire (Cerny et al 1983;Martinez-A. et al 1985;Coutinho et al 1987).…”

Section: (A) Consequences For Offspring Immune Functionmentioning

confidence: 99%

Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission

Grindstaff

Brodie

Ketterson

2003

Proc. R. Soc. Lond. B

339

412

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The past 30 years of immunological research have revealed much about the proximate mechanisms of maternal antibody transmission and utilization, but have not adequately addressed how these issues are related to evolutionary and ecological theory. Much remains to be learned about individual differences within a species in maternal antibody transmission as well as differences among species in transmission or utilization of antibodies. Similarly, maternal-effects theory has generally neglected the mechanisms by which mothers influence offspring phenotype. Although the environmental cues that generate maternal effects and the consequent effects for offspring phenotype are often well characterized, the intermediary physiological and developmental steps through which the maternal effect is transmitted are generally unknown. Integration of the proximate mechanisms of maternal antibody transmission with evolutionary theory on maternal effects affords an important opportunity to unite mechanism and process by focusing on the links between genetics, environment and physiology, with the ultimate goal of explaining differences among individuals and species in the transfer of immune function from one generation to the next.

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“…It is well known that neonatal injection of specific anti-T15 monoclonal antibodies led to a long-term suppression of B cells expressing the complementary Id. 13,14 However, at young/adult age the Id-suppressed mice were able to mount a robust, undiminished antibody response, but such a response was characterized by the lack of the dominant T15 Id. By this procedure we obtained a group of young BALB/c mice showing an idiotypic repertoire of the PCspecific response similar to that of D1.LP mice.…”

Section: Introductionmentioning

confidence: 99%

Autologous anti‐idiotypic antibody response is regulated by the level of circulating complementary idiotype

Borghesi

Nicoletti

1996

Immunology

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SUMMARYBALB/c mice injected with lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) predominantly responded with antibody molecules the vast majority of which expressed the public idiotype T15 and were directed to the immunodominant epitope phosphorylcholine (PC). However, after a single immunization with Pn vaccine young (3-month-old) BALB/c mice did not produce any specific anti-T15 antibody response. In contrast, young D1.LP mice were able to mount a specific anti-T15 response upon primary immunization with pneumococcal vaccine. The anti-PC response in the two mouse strains differed in that the proportion of antibody molecules that expressed the T15 idiotype for Pn-primed D1.LP mice showed a smaller proportion of PC-specific antibody expressing the T15 idiotype. Neonatal injection of anti-T15 monoclonal antibodies led to a long-term suppression of the PC-specific T15 B-cell clones but at young/adult age these mice maintained the ability to produce a normal amount of PC-specific antibody. Interestingly, the idiotypically-suppressed BALB/c mice mounted a significant anti-T15 response during the primary response to Pn. We interpreted these data as showing that the level of circulating idiotype may regulate the production of the complementary antiidiotypic antibody. In addition, in vitro experiments demonstrated that the lack of the anti-T15 response during primary antibody response in BALB/c mice is probably because of a state of tolerance that is regulated by T cells.

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Antibody response of mice following neonatal treatment with a monoclonal anti‐receptor antibody. Evidence for B cell tolerance and T suppressor cells specific for different idiotopic determinants

Cited by 19 publications

References 30 publications

Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission

Autologous anti‐idiotypic antibody response is regulated by the level of circulating complementary idiotype

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