The origin and antigen-dependent distribution of IgA-containing cells in the intestine.

Abstract

The aims of this paper were to establish the origin of cells producing IgA antibody to cholera toxoid in the lamina propria of the small intestine and to define the role of antigen in their distribution. The use of Thirty-Vella loops made it possible to restrict antigenic challenge to a defined segment of the intestine in rats which had been primed i.p. with toxoid in Freund's complete adjuvant. The anti-toxin-containing cells (ACC) which appeared in the draining thoracic duct lymph after challenge of a loop were almost all of IgA specificity and their numbers were proportional to the length of intestine exposed to antigen. The abolition of this cellular response which occurred when Peyer's patches (PP) were removed from a loop before challenge and the failure of mesenteric lymphadenectomy significantly to affect the response indicated that ACC originated exclusively from PP. Cell transfer studies showed that although nonrecirculating large lymphocytes gave rise to ACC in the lamina propria, some of the recirculating small lymphocytes also developed subsequently into ACC. Counts of ACC in the lamina propria of challenged loops were consistently greater than in nonchallenged loops although some ACC were always present in the latter. However, a time-course study on the appearance of ACC in the lamina propria of cannulated rats given a single dose of thoracic duct lymphocytes from immunized donors demonstrated that ACC continued to accumulate and persist in challenged loops but only appeared transiently in nonchallenged loops. These transients did not migrate from the lamina propria back into the lymph and they presumably died in situ. The increase in the number of ACC in loops which had been challenged with antigen was probably due both to cell division in the lamina propria and to the development of new ACC from recirculating lymphocytes which had been recruited into the loop. Thus, the cells which give rise to intestinal ACC can migrate into the lamina propria independently of antigen, but antigen has a profound effect on the location, magnitude, and persistence of the response.