Altered hepatic transport of immunoglobulin A in mice lacking the J chain.

Hendrickson, Barbara A.; Conner, David A.; Ladd, Daniel; Kendall, Donna; Casanova, James E.; Corthésy, Blaise; Max, Edward E.; Neutra, Marian R.; Seidman, Cynthia; Seidman, Jonathan G.

doi:10.1084/jem.182.6.1905

Cited by 133 publications

(97 citation statements)

References 35 publications

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“…To test this possibility, we employed two murine models, pIgR-and J chain-deficient mice, in which neither IgA nor IgM can be actively transported into the intestinal lumen, rendering the mice functionally double deficient for luminal IgA and IgM (11,14). The pIgR is expressed by intestinal epithelial cells and required for active transport of polymeric IgA and IgM into the lumen, while J chain is expressed in B cells and plasma cells and needed for the efficient formation of polymeric IgA and IgM and their transport into the lumen by pIgR.…”

Section: Resultsmentioning

confidence: 99%

“…J chaindeficient mice have an insertional mutation in the J chain gene, which disrupts production of functional J chains in B cells and thus efficient formation of polymeric antibodies (11). IgA and IgM are produced at normal levels in the mucosa, but the lack of associated J chain prevents their active transport into the intestinal lumen by pIgR (11), which makes these mice phenotypically similar to pIgR-deficient mice. IgG3-deficient mice have an insertional mutation/deletion in the ␥3 heavy-chain constant region locus, such that 54 bp of ␥3 CH1 domain is deleted, leaving the switch region intact (34).…”

Section: Methodsmentioning

confidence: 99%

“…pIgR-deficient mice have normal, high-level mucosal production of polymeric IgA and IgM but cannot actively transport these isotypes across the intestinal epithelium, so that their levels in serum are Ͼ20-fold increased (14). J chaindeficient mice have an insertional mutation in the J chain gene, which disrupts production of functional J chains in B cells and thus efficient formation of polymeric antibodies (11). IgA and IgM are produced at normal levels in the mucosa, but the lack of associated J chain prevents their active transport into the intestinal lumen by pIgR (11), which makes these mice phenotypically similar to pIgR-deficient mice.…”

Section: Methodsmentioning

confidence: 99%

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Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

et al. 2004

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Citrobacter rodentium, a murine model pathogen for human enteropathogenic Escherichia coli, predominantly colonizes the lumen and mucosal surface of the colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice infected with C. rodentium develop a secretory immunoglobulin A (IgA) response, but the role of B cells or secretory antibodies in host defense is unknown. To address this question, we conducted oral C. rodentium infections in mice lacking B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice showed peak bacterial numbers in colon and feces at 1 week and bacterial eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible initially but could not control infection subsequently. Tissue responses showed marked differences, as infection of normal mice was accompanied by transient crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6 weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6 weeks. The functions of B cells were not mediated by secretory antibodies, since mice lacking IgA or secreted IgM or proteins required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally. Nonetheless, systemic administration of immune sera reduced bacterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this effect. These results indicate that host defense against C. rodentium depends on B cells and IgG antibodies but does not require production or transepithelial transport of IgA or secreted IgM.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

et al. 2004

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“…1). Pools of "monomer" (fractions 4-8) and "polymer" (fractions [12][13][14][15][16][17][18][19][20] were concentrated by ultrafiltration and dialyzed against DPBS to remove sucrose, and their IgM concentrations were determined in ELISA. Insufficient SP-6 monomer was obtained for experiments so only the polymer was used.…”

Section: Immunoglobulinsmentioning

confidence: 99%

“…In this paper, we show that the T560 IgA/IgM receptor is pIgR based on the following evidence: its binding of IgM is inhibited by pIgA but not by S-IgA and is J chain dependent as is binding of pIg by human (16,17) and mouse (18) pIgRs; it binds IgM through a different structure from the distinct IgM receptor (Fc R) of mouse T cells (19); it is precipitable with either IgA or IgM; its M r (116 kDa) is consistent with its being pIgR; and it is recognized by Abs to mouse pIgR on immunoblots. Furthermore, complete mRNA for pIgR is contained in T560 cells.…”

mentioning

confidence: 99%

The IgA/IgM Receptor Expressed on a Murine B Cell Lymphoma Is Poly-Ig Receptor

Phillips‐Quagliata

Patel

Han

et al. 2000

The Journal of Immunology

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T560, a mouse B lymphoma that originated in gut-associated lymphoid tissue, expresses receptors that bind dimeric IgA and IgM in a mutually inhibitory manner but have little affinity for monomeric IgA. Evidence presented in this paper indicates that the receptor is poly-Ig receptor (pIgR) known in humans and domestic cattle to bind both IgA and IgM. The evidence includes the demonstration that binding of IgM is J chain dependent, and that pIg-precipitated receptor has an appropriate Mr of 116–120 kDa and can be detected on immunoblots with specific rabbit anti-mouse pIgR. Overlapping RT-PCR performed using template mRNA from T560 cells and oligonucleotide primer pairs designed from the published sequence of mouse liver pIgR indicate that T560 cells express mRNA virtually identical with that of the epithelial cell pIgR throughout its external, transmembrane, and intracytoplasmic coding regions. Studies using mutant IgAs suggest that the Cα2 domain of dimeric IgA is not involved in high-affinity binding to the T560 pIgR. Inasmuch as this mouse B cell pIgR binds IgM better than IgA, it is similar to human pIgR and differs from rat, mouse, and rabbit epithelial cell pIgRs that bind IgA but not IgM. Possible explanations for this difference are discussed. All clones of T560 contain some cells that spontaneously secrete both IgG2a and IgA, but all of the IgA recoverable from the medium and from cell lysates is monomeric; it cannot be converted to secretory IgA by T560 cells.

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Antibody against the human J chain inhibits polymeric Ig receptor‐mediated biliary and epithelial transport of human polymeric IgA

et al. 1998

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To emphasize the requirement for a J chain in native polymeric immunoglobulins for their selective transport into exocrine secretions, IgG, purified from two different antisera specific for the human J chain, was shown to: (i) bind in vitro to human polymeric IgA (pIgA) by density gradient ultracentrifugation; (ii) inhibit binding in vitro of rat secretory component to human pIgA; (iii) inhibit hepatic transport of human pIgA into rat bile in vivo; and (iv) inhibit apical transcytosis of pIgA in vitro by polarized human polymeric immunoglobulin receptor (pIgR)-expressing Madin-Darby canine kidney cells. Inhibition of biliary transport increased with the molar ratio of anti-J chain antibodies against pIgA and their incubation time. Anti-J chain F(ab')2 and Fab fragments also inhibited biliary transport, excluding a role for phagocytic clearance or excessive size of the immune complexes. Anti-human-Fc alpha Fab, bound to human pIgA in complexes of larger size than those with anti-J chain Fab, did not inhibit biliary transport of human pIgA. Propionic acid-denatured human pIgA, although containing J chains, was very poorly transported into rat bile. Altogether, our data strongly support, now also by in vivo experiments, the crucial role of the J chain of native pIgA in its selective pIgR-mediated transport into secretions, as suggested long ago by in vitro data only. Recent data on J chain-knockout mice, with low IgA levels in bile and feces, cannot explain the role of the J chain in contributing to the secretory component/pIgR-binding site of normal pIgA, but otherwise agree with our study.

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Altered hepatic transport of immunoglobulin A in mice lacking the J chain.

Cited by 133 publications

References 35 publications

Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

The IgA/IgM Receptor Expressed on a Murine B Cell Lymphoma Is Poly-Ig Receptor

Antibody against the human J chain inhibits polymeric Ig receptor‐mediated biliary and epithelial transport of human polymeric IgA

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