Cell Makeup Affects Immunity in the Elderly

In a study of transgenic mice, researchers from National Jewish Medical and Research Center (Denver CO, USA) found that as the body ages it becomes increasingly dependent on less effective antigen-experienced B cells. These do not counter infection as well as naive B cells, which predominate in younger individuals. The findings appear in the May 15, 2002, issue of The Journal of Immunology.

Researchers had been puzzled by the fact that although production of new B cells declines with age, the number of circulating B cells remains nearly constant. Dr. John Cambier and his colleagues hypothesized that older mice maintain high B-cell levels by stockpiling antigen-experienced B cells. Exposure to foreign pathogens helps them live longer than naive B cells, which usually die after five to six weeks if they do not encounter a pathogen.

Antibodies secreted by antigen-experienced B cells are made to fight a previous pathogen and generally do not bind strongly to the current one. Naive B cells can mount a more potent defense because they custom-tailor their antibodies to the current pathogen, allowing the antibodies to bind strongly.

The investigators examined the B cells in mice less than three months of age and mice older than 22 months. They used a number of cell characteristics, including cell-surface receptors and antibody expression, to distinguish antigen-experienced B cells from naive ones. One kind of naive B cell, called a follicular cell, decreased from an average of 70% of the B-cell population in young mice to 32% in older mice. In another analysis, results indicated that only about 5% of the B cells in young mice were antigen-experienced, but they accounted for 76% of the B cells in older mice. "These numbers are averages,” said co-author Sarah Johnson. "The B cell populations of individual mice varied, with some retaining large numbers of naive B cells and other carrying almost none. The mice with many naive B cells would presumably be better at fighting off infections.”

In a later study, hematopoietic stem cells from young mice were transplanted into old mice. Initial results suggest that the transplantation restores the B cell population to a younger, more naive and adaptable profile.




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