ISSN:0304-324X    

DOI:10.1159/000212704

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Proposed relationships of DNA repair, mutation, and the process of generation of antibody diversity allow new insights into the mechanism of aging. Pathways of antibody development are reviewed with special attention to steps which generate diversity. The normal process of combinatorial fusion of V region gene segments (i.e. V, D, and J) coding for the entire V region, plus the somatic variation within the fusing sites, appear to be enough to account for adequate antibody diversity without a hypermutation mechanism. We propose that the somatic hypermutation commonly observed in antibody V regions may have limited usefulness to expand the diversity of the antigen-binding capacity of the individual. Rather, such mutation may serve as a time clock for aging. Knowledge about humans with specific abnormal repair and/or mutation functions will allow testing of this proposal.

ISSN:0304-324X    

DOI:10.1159/000212705

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Investigations into mechanisms by which macrophages distinguish mature from senescent self revealed that a Mr ∼ 62,000 glycoprotein, the senescent cell antigen, appears on the surface of senescent and damaged cells. It is recognized by the antigen-binding Fab region of a specific IgG autoantibody in serum which attaches to cells carrying the senescent cell antigen and initiates their removal by macrophages. The senescent cell antigen was first observed on the surface of senescent human erythrocytes but has since been demonstrated on all cells examined. Senescent cell antigen appears to be derived from band 3, the major anion transport protein of the erythrocyte. The current working hypothesis is that degradation of band 3 causes a conformational change in its tertiary structure that generates the senescent cell antige

ISSN:0304-324X    

DOI:10.1159/000212706

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Aging is accompanied by increased prevalence of serum autoantibodies. One commonly detected autoantibody, IgM rheumatoid factor, is also found associated with rheumatoid arthritis and other autoimmune disorders. Much evidence indicates that this autoantibody plays a physiologic role in the immune response. The potential of human subjects to secrete this autoantibody and the age-related changes in its expression by human peripheral blood and bone marrow lymphocytes have been investigated. The size of this self-reactive B cell pool increases with advancing age. The lymphocytes expressing this potential are found predominantly in an early B cell subset in elderly individuals as compared to a more mature B cell subset in individuals with rheumatoid arthritis. Preliminary data show that IgM rheumatoid factors share idiotypes implying a common origin, possible from a single light chain gene or a closely related family of light chain genes.

ISSN:0304-324X    

DOI:10.1159/000212707

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

In the present study, we examined the changes that occur with age in anti-idiotype-blocked, hapten-augmentable PFC in the mucosal-associated lymph nodes (MLN and BLN) and spleen of various strains of mice. 2-month-old 129/J, AKR/J, and C57L/J mice had a high percentage of hapten-augmentable PFC in their spleen, MLN, and BLN; however, by 6–11 months these values had declined considerably in the spleen, while mucosal values remained high. In contrast, 2-month-old C57BL/6J, DBA/2J, and C3H/HeJ mice had a low percentage of hapten-augmentable PFC in their spleen, MLN, and BLN; but by 6–11 months these values had increased considerably in the spleen, while mucosal values remained low. CBA/J and SJL/J mice maintained high and low levels, respectively, of hapten-augmentable PFC in their spleens, MLN, and BLN over the age span. NZB/BinJ mice were found to be low producers in the spleen, but high in the MLN and BLN at 2 and 6 months of age. These data indicate that there are strain differences in the development of auto-anti-idiotypic antibody regulation with

ISSN:0304-324X    

DOI:10.1159/000212708

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Recent data point to a significant role for thymosins, lymphokines, and other soluble mediators in the senescence of the immune response that occurs with aging. In recent years, considerable progress has been made in the isolation and physiochemical characterization of several of these soluble mediators. We are now beginning to define the mechanisms by which these molecules regulate and mediate immune responses. In this paper we review the properties of the best characterized thymic hormones and lymphokines and focus on the role of the endocrine thymus in modulating immune responses. Of particular interest is the recent observation that thymosin fraction 5 can enhance production of interleukin-2 (IL-2) and colony-stimulating factor (CSF), and that IL-2 production, but not CSF production, is selectively diminished in aging mice. Several of the products of the immune system also can act as neuroactive immunotransmitters and modulate a number of neuroendocrine responses. Current studies point to an important role for these molecules in modulating neuroendocrine function, suggesting a broader role for the endocrine thymus in the aging process.

ISSN:0304-324X    

DOI:10.1159/000212709

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

An assay was developed for studying the effect of age on human colony-forming T and B cells. Phytohemagglutinin was used to induce the formation of T cell colonies and anti-human Fab antibodies were used to induce the formation of B cell colonies. The assay requires a short ( < 8 h) incubation in liquid media in the presence of a mitogen prior to plating in semisoft agar. Neither autologous serum, red cells, nor conditioned media are required to support colony formation. The kinetic and morphologic characteristics of T and B cell colonies were different. Formation of T cell macro- but not microcolonies was significantly impaired during aging. Formation of B cell colonies was decreased with aging, but the decrease was not significant.

ISSN:0304-324X    

DOI:10.1159/000212710

出版商:S. Karger AG    

年代:1985

数据来源: Karger