Peripheral T Cells Select the B‐Cell Repertoire in Old Mice
- 1 August 1989
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 110 (1) , 173-185
- https://doi.org/10.1111/j.1600-065x.1989.tb00033.x
Abstract
These studies have shown that the alterations in the repertoire of antibody produced by old mice is not due to an intrinsic defect in the bone marrow or in the B-lymphocyte population arising from the bone marrow but rather to a selective downregulation by auto-anti-idiotypic antibody and idiotype-anti-idiotype interactions, shifting the idiotype distribution in the peripheral B-cell population. Thus, the clonal distributions of B cells generated by bone marrow of old and young mice are very comparable. The age-related differences in antibodies expressed by young and old mice are, to a great extent, determined by the activity of a peripheral regulatory immune network. This immune cellular network operates prior to exposure to antigen, presumably on the basis of an idiotype-anti-idiotype network between T and B lymphocytes. After exposure to antigen, a network of idiotype-anti-idiotype antibody interactions also contributes to differences in the immune responses of old and young mice to foreign antigens. If the expressed repertoire of antibody reflects down-regulation of auto-anti-idiotypic antibody, comparable repertoires of B-cell clones would be expected to be recovered from old and young mice if B cells from old mice were rescued from selective peripheral downregulatory influences active in old mice. Support for this hypothesis has been obtained by generating B-cell hybridomas from young and old mice immunized with TNP bovine gamme globulin (Marcenario et al. 1989). The same number of anti-TNP hybridomas and a comparable number of IgG and high-affinity antibody-producing clones were recovered from the spleens of young and old mice. Thus, the actual B-cell clonal repertoires of young and old mice appear to be similar although the expressed repertoires of antibody-producing lymphocytes from old and young mice are very different. This conclusion has considerable impact on strategies that could be employed to reverse the senescence of humoral immunity. Strategies to counter downregulatory influences which constrain the expression of the B-cell population should be more effective than attempts to reconstitute the repertoire of B lymphocytes in aged individuals. Finally, the mechanisms underlying these age-associated shifts in the expressed humoral antibody response can be attributed to life-long interactions with self and foreign antigens. The overall shift may be described as a decreased reactivity to foreign antigens and a complementary increase in reactivity with self antigens.(ABSTRACT TRUNCATED AT 400 WORDS)Keywords
This publication has 22 references indexed in Scilit:
- Immunological studies of agingCellular Immunology, 1989
- Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice.The Journal of Experimental Medicine, 1985
- Ultimate erythropoietic repopulating abilities of fetal, young adult, and old adult cells compared using repeated irradiation.The Journal of Experimental Medicine, 1984
- Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses.The Journal of Experimental Medicine, 1984
- Production of auto-antiidiotypic antibody during the normal immune response. VII. Analysis of the cellular basis for the increased auto-antiidiotype antibody production by aged mice.The Journal of Experimental Medicine, 1983
- Loss of immune competence with age may be due to auto-anti-idiotypic antibody regulationNature, 1980
- Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. II. Hapten-reversible inhibition of anti-TNP plaque-forming cells by immune serum as an assay for auto-anti-idiotypic antibodyThe Journal of Experimental Medicine, 1979
- Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. I. Occurrence in AKR/J and BALB/c mice of hapten-augmentable, anti-TNP plaque-forming cells and their accelerated appearance in recipients of immune spleen cellsThe Journal of Experimental Medicine, 1979
- Immunological studies of aging. IV. The contribution of thymic involution to the immune deficiencies of aging mice and reversal with thymopoietin32-36.The Journal of Experimental Medicine, 1978
- THE PRESENCE OF HETEROPHILE ANTIBODIES IN INFECTIOUS MONONUCLEOSISThe Lancet Healthy Longevity, 1932