Impaired humoral immune responsiveness is frequently observed during aging and is a determinant of the increased morbidity and mortality of elderly persons due to infections. Reports investigating the functions of B cells form elderly persons have clearly described alterations of proliferation and impairments in differentiation. However nothing is known about the mechanisms of human B cell dysfunctions during aging. Methodologies to precisely analyze the proliferation and differentiation of human B cells without dependency on T cells or monocytes are operational in our laboratories. Our results indicate that human B cell subsets can be distinguished by surface markers and functions. Other data support the concept that aberrancies of B cell functions with aging represent selective a normalities within subsets rather than generalized dysfunctions. The overall goals of this project are to attempt to determine the mechanisms which are responsible for human B cell dysfunction during aging and to identify approaches which can possibly help improve the reduced function of B cells from elderly persons. We will accomplish these goals by assessing the proliferative and differentiative capabilities of B cells from elderly persons directly activated in the presence of B cell growth factors, differentiation factors, and specific lymphokines.
The specific aims are: 1) to determine if aging may affect the frequencies or functions of human B cell subsets bearing surface markers recognized by monoclonal antibodies (MoAG); 2) to study whether the reduced functional capabilities of B cells represent altered expression or regulation of IL 2 receptors (IL 2R) or transferrin receptors (TR); 3) to analyze if aberrancies of the B cell growth factor (BCGF) auotcrine network may be important in the dysfunction or B cells from elderly persons and 4) to investigate whether the reduced activation/differentiation of B cells from elderly persons represents decreased responsiveness to specific lymphokines or an increased sensitivity to inhibition. The requirements and responsiveness of B cells from elderly subjects will be compared to B cells from young subjects. The results to be obtained by the direct investigations of human B cells during aging are anticipated to provide precise answers about the mechanisms of B cell dysfunction during aging. These answers are important in better understanding how aging affects the B cell system and may also be of clinical importance.
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