The aging effect on the quantity of intestinal IgA and IgM class-specific immunoglobulins secreted and the quality of intraluminal intestinal IgA was studied in 5- to 6-month-old and 24- to 28-month-old male BALB/c mice. The level of IgA increased in the intestinal juice from the aged mice, while the IgM level remained unchanged. These alterations were similar to those found in serum, but the effect of age on serum IgA was profound, almost a threefold increase, in contrast to an increase of just under 35% in intestinal secretions. The ratio of dimeric to total IgA in the small intestine decreased in the older mice, though that of serum was unchanged. In contrast, the total amounts of dimeric IgA in the small intestinal lavage fluid did not change between the two age groups, while the dimeric IgA in serum in older mice were 4.5 times as high as those of young mice. The binding of purified intestinal dimeric IgA to antigens from normal habitant enteric bacteria (gamma streptococci and Enterobacter agglomerans) declined in the old mice. In the immunochemical studies, using SDS-PAGE and isoelectric focusing, the purified intestinal IgA from the young and old mice showed no major differences. Thus, the findings in aged small intestinal perfusates that the increased content of intraluminal IgA is due to an increased monomeric IgA, but not to a reduced dimeric IgA, which remains unchanged, and that the binding capacity of the dimeric IgA to the bacterial antigens is diminished, suggest that the level of the natural secretory IgA antibody is decreased. These altered quantitative and functional features of intraluminal intestinal IgA observed in the aged mice appear to be due to the complex heterogeneous effects of senescence on gut-associated lymphoid tissues, and may contribute to age-related impairment in gut humoral immune function.

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Gut mucosal immunoglobulin (Ig) isotype expression and secretion are known to be regulated by B cell-stimulatory factors (BSF), lymphokines or cytokines from T and non-B cells. The class and amount of Ig secreted appear to depend on the presence of a combination of these factors. The effects of IL-4 and IL-5 on Ig class switching by gut mucosal B cells remain controversial. To shed further light on this issue, young (1-2 months old) athymic nu/nu murine GALT B cells were chosen, because the possibility of in vivo effects of T cells on B cells (in particular at the levels of transcription and translation without changes in surface Ig phenotype expression) cannot be excluded. The results are summarized below. IL-4, IL-5 and IL-6 alone or in combination do not act as IgA heavy chain switch cofactors, but IL-5 and IL-6 do act at least as B cell terminal differentiation factors for any isotype-specific gut-associated lymphoid tissue (GALT) (mesenteric lymph node) B cells in the presence or absence of LPS. The BSF have augmenting effects on class-specific Ig production by GALT sIgM-bearing B cells, when these are treated with the BSF alone. IL-4 alone or in combination with other BSF prevents LPS-stimulated IgM production. BSF without LPS do not evoke production of significant amounts of IgG and IgA by high density (HD) and low density (LD) sIgM-bearing B cells; IgM is synthesized only in small amounts of LD sIgM-bearing B cells in the presence of IL-5 and/or IL-6. There is no difference in the responsiveness of GALT and spleen sIgM-bearing B cells to the BSF.