Age-Associated Changes in Antibody-Forming Cells (B Cells)

Conclusion

Despite considerable experimental effort, it is not possible to state unequivocally that with aging there occur some intrinsic changes in B cells. We have some indication that the number of pre-B cells may be affected in the bone marrow of the aged. If these changes extend to a decrease of the actual number of pluripotent stem cells, then this would indeed contribute to a lack of self-renewing capacity and affect the total peripheral B cell population. In those instances when actual precursor cell frequencies have been enumerated, even though for the majority of antigen systems studied B cell precursor frequency decreases in the aged, the responding B cells showed no individual functional decline (i.e., amount of antibody synthesized). Evidence has been obtained that changes in regulatory mechanisms are responsible, in part, for the decline in the immune response of the aged. This is particularly obvious when V_H gene usage in antibody is compared between the total available repertoire (i.e., following B cell polyclonal activation) and that seen after antigen stimulation. The T cell compartment plays an important role in the expression of the antibody repertoire in both the young and the aged (77). Thymic involution, decrease in T cell function, and changes in T cell receptor repertoire may lead to altered T cell regulation as the animal senesces.

We have presented evidence that in aging there is a decrease in the magnitude of antibody responses to both thymic-independent and TD antigens. There is also a decline in the affinity of antibody produced to TD antigen. An age-related change in antibody repertoire has been documented at both the serologic and molecular levels. Changes in regulatory mechanisms involving T cells and the immune network have also been described. Along with all of these changes, an intrinsic alteration in B cells may also occur in senescence. Both intrinsic and regulatory changes may contribute to the immune response as seen in the aged.