Differentiated B lymphocytes. Potential to express particular antibody variable and constant regions depends on site of lymphoid tissue and antigen load

Abstract

B cells have the potential to respond to an antigen by producing antibodies with a variety of variable and constant regions. We have quantitatively analyzed B-cell potential at the single cell level to determine the effect of lymphoid tissue site and antigen load on the expression of variable and constant regions. Concerning variable region expression, although the total frequency of B-cell precursors for phosphorylcholine is similar between nonimmune spleen and gut-associated Peyer's patch tissues, the proportion of cells producing non-TEPC 15 idiotypes is greater from Peyer's patch than from spleen. Oral immunization with phosphorylcholine-containing Ascaris suum increased the frequency of non-TEPC 15 B cells. Thus variation in the proportion of cells bearing different variable regions may be related to the distinct antigenic environment of cells in Peyer's patches compared to that of cells in spleen. Regarding constant region expression, although B cells from both spleen and Peyer's patches generate clones producing IgM, IgGl, and IgA singly and in all combinations, cells from Peyer's patches generate more clones secreting only IgA than cells from spleen. B cells specific for phosphorylcholine and inulin, which are found on intestinal bacteria, produce more IgA-only clones than B cells specific for the dinitrophenyl determinant. This striking correlation between IgA expression and variable region specificity for antigen implies that environmental antigens have expanded certain B cells in Peyer's patches which then have the ability to generate progeny that express only IgA. Evidence supporting the secondary nature of precursors for IgA-only clones is obtained by their ability to produce this isotype after stimulation with histoincompatible T cells. The role of gut antigens may be to clonally expand IgA precursors and perhaps to stimulate the proliferation of less differentiated cells within the unique microenvironment of the Peyer's patches, allowing them to differentiate to IgA precursors.