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

Abstract

The lamina propria of the intestine contains large numbers of IgA-producing plasma cells which arise from precursors in the gut-associated lymphoid tissue (GALT) 1 in response to antigens in the lumen of the gut (1). The precursors are large lymphocytes which travel from the GALT to the blood in the thoracic duet lymph and then migrate into the lamina propria where they secrete IgA antibody (2-4). The mechanism of this selective migration into the lamina propria is not known and, in particular, there is controversy about the role of antigen in determining the distribution of IgA-secreting cells along the intestine.It has been reported that radiolabeled large lymphocytes from adult syngeneic donors will migrate into the intestinal lamina propria of neonatal rats (5) and into fetal intestine grafted under the kidney capsule of adult mice (6). These experiments with "antigen-free" gut are held to show that factors other than antigen determined the gut-homing of large lymphocytes. On the other hand, Ogra and Karzon (7) showed that local immunization of a segment of human colon with polio vaccine was followed by the appearance of specific IgA antibody which was entirely confined to the immunized segment. Husband and Lascelles (8) reported similar findings in sheep with two Thiry intestinal loops. When different antigens were administered into each loop, IgA antibody against each of the antigens appeared only in the correspondingly immunized loop and never in both loops. In these studies antigen appeared to be decisive in determining the localization of the blood-borne IgA precursors. Similar contradictions were reported by Pierce and Gowans (4). In immunized rats, the density of cells in the lamina propria producing IgA antibody against cholera toxoid was always highest in that region of the intestine which had been challenged with antigen. On the other hand, the small intestine of nonimmunized rats rapidly accumulated anti-toxin-containing cells (ACC) after an intravenous injection of lymphocytes obtained from the thoracic duet of immunized donors.In an attempt to reconcile these contradictory reports the colonization of the lamina propria with specific antibody-producing cells has been studied under more defined conditions using Thiry-Vella intestinal loops in rats and cholera toxoid as antigen. The results indicate that the accumulation of ACC in the gut is probably the result of both antigen-dependent and independent processes.

Chromosomal translocations deregulating c-myc are associated with normal immune responses

“…These sequences are available from EMBL/GenBank/DDBJ under accession numbers U67968 ± U67983. Translocations denoted BPI and DPI are from Peyer's patches of immunized BALB/c and DBA/2 mice, and BPS and DPS from control BALB/c and DBA/2 mice, respectively , 1977;Husband and Gowans, 1978;Stanton et al, 1983;Strober et al, 1991). Second, the frequency of translocations signi®cantly increases upon gut immunization with cholera toxin, an antigen which induces a predominant IgA response (Table 1) (Lycke and Holmgren, 1986;Lycke and Strober, 1989).…”

“…Calculation of translocation frequencies (Table 1) Sensitivity of assay, left, Equimolar mixtures of S107 and T1165 DNA with characterized c-myc/IgA translocations were diluted to contain a calculated single translocation copy of each per reaction mixture. Ampli®ed samples were electrophoresed on agarose gels and stained with ethidium bromide, right, DNA from three tumors (S107, M315 and T1165) at three copies per reaction mixture were ampli®ed individually or as a pool to demonstrate detection of di erent translocations (Craig and Cebra, 1971;Husband et al, 1977;Husband and Gowans, 1978;Strober et al, 1991). Such cells are then thought to seed other organs (Husband et al, 1977;Husband and Gowans, 1978) including the mesenteric lymph node.…”

“…Ampli®ed samples were electrophoresed on agarose gels and stained with ethidium bromide, right, DNA from three tumors (S107, M315 and T1165) at three copies per reaction mixture were ampli®ed individually or as a pool to demonstrate detection of di erent translocations (Craig and Cebra, 1971;Husband et al, 1977;Husband and Gowans, 1978;Strober et al, 1991). Such cells are then thought to seed other organs (Husband et al, 1977;Husband and Gowans, 1978) including the mesenteric lymph node. We, therefore, assessed the e ect of gut immunization with cholera toxin, an antigen known to produce a predominant IgA response (Lycke and Holmgren, 1986;Lycke and Strober, 1989), on the occurrence of translocations.…”

Alternate Mucosal Immune System: Organized Peyer’s Patches Are Not Required for IgA Responses in the Gastrointestinal Tract

“…The importance of Peyer's patches in the induction of mucosal Ab responses has been shown in the rabbit model where the lamina propria of intestine contains IgA-secreting plasma cells that arose from precursors in the Peyer's patch (3). Further, Ag-specific IgA precursors from Peyer's patches repopulated in the lamina propria with differentiation into IgA-producing plasma cells (33). In addition, introduction of Ags into the surgical constructed intestinal loops that bore a Peyer's patch resulted in the appearance of S-IgA Abs after immunization of Ag, whereas no mucosal responses were detected in intestinal loops that lacked visible Peyer's patches (34).…”

Eosinophilia is attenuated in experimental colitis induced in IL-5 deficient mice

“…The average number of cells per scan was expressed as cells per linear cm of intestine by multiplying by 30.3, a correction factor determined from the field width of 330 m, as previously described. 20 …”