Influences of the microenvironment on B-cell responses of wasted mice: comparison of Peyer's patches and mesenteric lymph nodes.

Wasted mice bear an autosomal recessive mutation (wst/wst) that gives rise to neurologic abnormalities and immunologic deficiency evident as early as 21 days of age. Features of the immune deficiency include absence of plasma cells at mucosal sites, reduction in weight of thymus and spleen relative to body weight, and low serum levels of some immunoglobulin (Ig) isotypes. In these experiments, we have examined parameters of B-cell function in Peyer's patches (PP) and mesenteric lymph nodes (MLN) of wst/wst and age-matched control mice. Our results established the following abnormalities in PP but not MLN of wst/wst mice relative to controls: (1) reduced mitogenic responses to lipopolysaccharide, (2) decreased percentages of Ig+ cells, (3) increased percentages of B-cells bearing large amounts of surface Ig ("very bright" Ig+ cells), and (4) reduced levels of all Ig-specific messenger ribonucleic acids (mRNAs) except alpha-mRNA. The only immunologic abnormality consistently expressed in lymphocytes from both MLN and PP of wst/wst mice is reduced levels of IgA+ B cells and alpha-mRNA. Morphologic studies revealed no consistent abnormalities in lymph nodes, spleens, livers, or PP of wst/wst mice when compared to littermate controls. These results support the idea that some of the immunologic abnormalities reported in wst/wst mice are due to microenvironmental influences. Of the parameters examined in this report, only reduced IgA (mRNA levels and percentage of positive cells) is consistently observed in PP, MLN, and spleen.