First Medawar prize lecture. The recirculating small lymphocyte.
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Awards and Prizes↗
Biomedical subjects
J L Gowans
Publications and source records attributed to J L Gowans.
The origin and antigen-dependent distribution of IgA-containing cells in the intestine.
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.
Animals↗
Cellular mediators of allograft immunity.
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Animals↗
Nature of cells binding anti-IgE in rats immunized with Nippostrongylus brasiliensis: IgE synthesis in regional nodes and concentration in mucosal mast cells.
The possibility that IgE is a secretory immunoglobulin has been examined by studying the tissue and cellular localization of IgE in rats infested with the enteric parasite, Nippostrongylus brasiliensis. The lamina propria of the small intestine and the colonic and pulmonary mucosal surfaces contained numerous anti-IgE-binding cells, but these were shown to be mast cells and not plasma cells. The major site of IgE synthesis was the regional lymph node of the small intestine, the mesenteric node, which contained large numbers of IgE-secreting plasma cells. Smaller numbers of IgE-secreting plasma cells were also found in the axillary node, which drained the site of larvae injection. Peyer's patches, the intrapulmonary bronchial lymphoid tissue and the spleen contained few, if any, IgE-secreting plasma cells. The significance of the IgE which was readily demonstrated in germinal centers of the mesenteric lymph nodes, the Peyer's patches and the axillary lymph nodes, is not known. In contrast to the infested animals, the lymphoid organs of normal rats rarely contained any IgE-CONTAINING CELLS; An unexpected observation was that mast cells in mucosal organs appear to contain intracellular IgE, differing in this respect from connective tissue mast cells. Mast cells lying between epithelial cells, the "globule leukocytes", also appear to contain intracellular IgE, and it is suggested that such cells may be responsible for the presence of IgE in exocrine secretions. This study does not support the suggestion that IgE is a secretory immunoglobulin with a physiology analogous to that of IgA.
Animals↗
Cellular kinetics of the intestinal immune response to cholera toxoid in rats.
The aims of this study were (a) to find a regime of immunization with cholera toxoid in rats which would establish a high density of antitoxin containing cells (ACC) in the lamina propria of the intestine and (b) to determine the origin of the ACC. The best cellular response was achieved by a single i.p. dose of toxoid in FCA followed by an intraintestinal boost 2 wk later. ACC appeared in the thoracic duct lymph 2 days after boosting, reaching a peak of about 200,000 ACC/h at 3--4 days. This was followed by the appearance of large numbers of ACC in the intestine. The i.p. dose of toxoid by itself gave rise to very few ACC in the gut or thoracic duct lymph, but it had clearly primed the gut immune system for a secondary response. Priming was also achieved by the prolonged oral intake of toxoid. The importance of the intestinal route for boosting was shown by the failure of i.p. challenge to give an ACC response in the intestine after i.p. priming and the small response it provoked after oral priming. ACC among thoracic duct lymphocytes (TDL) and in the lamina propria contained predominantly IgA. Two observations indicated that the major source of the lamina propria ACC was from cells that emerged in the thoracic duct lymph after intraintestinal challenge. Firstly, the establishment of a thoracic duct fistula immediately before challenge prevented the appearance of ACC in the intestine. Secondly, many ACC appeared in the intestine of normal rats after the injection of TDL rich in ACC. Although homing of ACC precursors to the gut was not antigen-dependent, the distribution of ACC in the lamina propria was considerably influenced by the site of the intestinal challenge, the density of ACC being greatest at or distal to the site of injection of toxoid into the lumen of the gut.
Animals↗
The presence of IgA on the surface of rat thoractic duct lymphocytes which contain internal IgA.
The presence of lymphocytes with internal IgA among cells from rat thoracic duct lymph wdy. The number of cells detected was greater in animals kept in a convential animal house compared with those maintained under specific pathogen-free conditions. Thoracic duct lymph from B rats and adult thymectomized rats also contained cell with internal IgA. The surface Ig of the IgA-containing cells was studied using a double-labeling technique with (126I) anti-Ig to detect surface Ig, and fluorescein-conjugated anti-IgA in large amounts, but very little IgM and no surface IgG2. The surface IgA was not acquired passively.
Animals↗
The origin and development of lymphocytes.
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Animals↗
The natural history of the cells producing IgA in the gut.
The IgA-secreting cells in the lamina propria of the small intestine are derived from large lymphocytes which enter the blood by way of the thoracic duct and then migrate into the gut where they complete their differentiation into plasma cells. Three aspects of this cellular traffic have been examined in rats. 1. The cells in thoracic duct lymph which give rise to IgA-secreting cells in the lamina propria are among those which carry surface IgA. Blast cells lacking surface immunoglobulin migrate mainly into the Peyer's patches and do not contribute to the IgA response. 2. Studies on a secondary antibody response to cholera toxoid, in which the challenge was given into a Thiry-Vella loop, showed that the antibody-containing blast cells in thoracic duct lymph were derived from Peyer's patches. The mesenteric nodes contributed little, if anything, to the cellular response in the lymph. 3. The idea that secretory component is a signal for the emigration of large lymphocytes from the blood into the lamina propria lacks experimental support. Secretory component does not bind to the IgA on the surface of thoracic duct cells. On the other hand, antigen in the gut may play an important part in immobilizing large lymphocytes in the lamina propria once they have migrated.
Animals↗
Subpopulations of B lymphocytes and the carriage of immunological memory.
Thoracic duct lymphocytes from rats primed with DNP-BGG confer on irradiated, syngeneic recipients the ability to mount a large, IgG anti-DNP response after challenge with the immunizing conjugate. An analysis of this adoptive response lead to the following conclusions. the B memory cells which generate the IgG response carry IgG on their surface and are present in a subpopulation amounting to less than l0% of all B cells in thoracic duct lymph. The view that memory cells carry exclusively IgD is untenable. The majority of B lymphocytes in thoracic duct lymph are recirculating cells which carry surface IgM...
Animals↗