Old mice recover the ability to produce IgG and high-avidity antibody following irradiation with partial bone marrow shielding.

Tsuda, Tadaaki; Kim, Young Tae; Siskind, Gregory W.; Weksler, Marc E.

doi:10.1073/pnas.85.4.1169

Cited by 14 publications

(4 citation statements)

References 16 publications

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“…We suggested that the senescence of humoral immunity resulted from the influence of the long-lived peripheral T cells on the population of B cells emerging from the bone marrow. This conclusion was consistent with the re-expression of a "young-like" antibody repertoire in old mice whose peripheral T cells had been destroyed by lethal irradiation and whose immune system had been autoreconstituted from their own bone marrow thai had been shielded from radiation damage (10). We concluded ourreviewin 1989 by writing, "the alterations in the repertoire of ami body produced by old mice is not due to an intrinsic defect in the bone marron or in the B lymphocyle populations orisind from the bone marrow but ralher ID a selective downregulation by fluio-anti-idiotypic antibody which shift the idid type distribution of the peripheral B cell population" (7).…”

Section: Introductionsupporting

confidence: 79%

Effect of age on humoral immunity, selection of the B‐cell repertoire and B‐cell development

LeMaoult¹,

Szabo²,

Weksler³

1997

Immunological Reviews

169

121

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The age-associated changes in humoral immunity affect the quality more than the quantity of the antibody response. Changes in the quality of the antibody response with age include shifts in antibody specificities from foreign to autoantigens, in antibody isotypes from IgG to IgM, in antibody affinities from high to low and in the antibody idiotypic repertoire. These changes can be traced to an impaired capacity of T cells to facilitate: (a) the maturation of B cells with respect to isotype and affinity maturation in the periphery and (b) the development of a diverse B-cell repertoire from precursors within the bone marrow. In contrast, there is no evidence that the amount of immunoglobulin produced before or after immunization diminishes with age. Nonetheless, the impaired responses of the elderly to most vaccines and the greater susceptibility of the elderly to infections has fostered a view that immune senescence leads to a state of immune deficiency. However, it is more precise to describe immune senescence as leading to a state of immune dysregulation. The dysregulation of the humoral immunity is manifested by a shift from adaptive humoral immunity, characterized by the production of a highly specific, high-affinity, IgG antibody response to foreign antigens, to a process of natural antibody-mediated immunity, dominated by low-affinity, polyreactive, IgM antibodies which react with autoantigens. Age-associated T-cell impairments appear to be the basis for the shift from adaptive to natural humoral immunity and their reversal should permit the restoration of an adaptive antibody response in the elderly.

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Section: Introductionsupporting

confidence: 79%

Effect of age on humoral immunity, selection of the B‐cell repertoire and B‐cell development

LeMaoult¹,

Szabo²,

Weksler³

1997

Immunological Reviews

169

121

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“…47 On the other hand, experiments in old mice have shown that full reconstitution of B-cell function is possible after irradiation with partial bone marrow shielding. 48 It seems likely, therefore, that a decline in B-cell output from the marrow is not a major determinant of impaired B-cell function in the elderly.…”

Section: B-lymphocyte Kinetics 3637mentioning

confidence: 99%

B-cell kinetics in humans: rapid turnover of peripheral blood memory cells

Macallan

Wallace

Zhang

et al. 2005

Blood

162

114

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Information about the kinetic behavior and lifespan of lymphocytes is crucial to understanding the mechanisms that regulate processes such as immunologic memory. We have used in vivo labeling of dividing cells with 6,6-2 H 2 -glucose, combined with cell sorting and gas-chromatography-mass spectrometry for deuterium enrichment, in order to analyze the kinetics of human total, naive, or memory B lymphocytes, separated from peripheral blood using monoclonal antibodies. We show that total blood B cells of young adults divide at an average rate of 1.9% (؎1.0%) per day and at a similar though slightly slower rate, 1.5% (

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“…and bone marrow reconstituted the periphery together with T cells from young or aged donors. It was found that mice that received young T cells displayed auto-anti-idiotypic antibody profiles and a response to TNP-F like that of the young donor (61,62), whereas those that received aged T cells responded like the aged donors (61,62). These results strongly implicate the T cells in the quantity and quality of the immune response.…”

Section: Bone Marrow and Agingmentioning

confidence: 62%