| First Author | Lycke N | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 2 | Pages | 913-9 |
| PubMed ID | 10395687 | Mgi Jnum | J:56158 |
| Mgi Id | MGI:1340167 | Doi | 10.4049/jimmunol.163.2.913 |
| Citation | Lycke N, et al. (1999) Lack of J chain inhibits the transport of gut IgA and abrogates the development of intestinal antitoxic protection. J Immunol 163(2):913-9 |
| abstractText | Recent publications have provided confusing information on the importance of the J chain for secretion of dimeric IgA at mucosal surfaces. Using J chain-deficient (J chain-/-) mice, we addressed whether a lack of J chain had any functional consequence for the ability to resist challenge with cholera toxin (CT) in intestinal loops. J chain-/- mice had normal levels of IgA plasma cells in the gut mucosa, and the Peyer's patches exhibited normal IgA B cell differentiation and germinal center reactions. The total IgA levels in gut lavage were reduced by roughly 90% as compared with that in wild-type controls, while concomitantly serum IgA levels were significantly increased. Total serum IgM levels were depressed, whereas IgG concentrations were normal. Following oral immunizations with CT, J chain-/- mice developed 10-fold increased serum antitoxin IgA titers, but gut lavage anti-CT IgA levels were substantially reduced. However, anti-CT IgA spot-forming cell frequencies in the gut lamina propria were normal. Anti-CT IgM concentrations were low in serum and gut lavage, whereas anti-CT IgG titers were unaltered. Challenge of small intestinal ligated loops with CT caused dramatic fluid accumulation in immunized J chain-/- mice, and only 20% protection was detected compared with unimmunized controls. In contrast, wild-type mice demonstrated 80% protection against CT challenge. Mice heterozygous for the J chain deletion exhibited intermediate gut lavage anti-CT IgA and intestinal protection levels, arguing for a J chain gene-dosage effect on the transport of secretory IgA. This study unequivocally demonstrates a direct relationship between mucosal transport of secretory SIgA and intestinal immune protection. |
