Immunochemical Studies on Free and Bound J Chain of Human IgA and IgM

Brandtzæg, Per

doi:10.1111/j.1365-3083.1975.tb02649.x

Cited by 50 publications

(43 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To further investigate the molecular nature of the two differently sized IgA molecules in the dimeric IgA fraction, we performed Western blotting with a specific anti-J chain antiserum (20,21). Anti-J chain specifically detected the upper 350-kDa dimeric IgA band in Western blot, but not the CD89-IgA complex (Fig.…”

Section: Iga-cd89 and Iga-j Chain Complexes Can Be Distinguished In Dmentioning

confidence: 99%

FcαRI/CD89 Circulates in Human Serum Covalently Linked to IgA in a Polymeric State

Boog

Zandbergen

Fijter

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

The FcR for IgA CD89/FcαRI, is a type I receptor glycoprotein, expressed on myeloid cells, with important immune effector functions. In vitro CD89 can be released from CD89-expressing cells upon activation. Little information is available on the existence of this soluble molecule in vivo. Using specific and sensitive ELISA techniques (detection limit 50 pg/ml), we were not able to detect circulating CD89 in human sera. However, using Western blotting, a 30-kDa soluble CD89 molecule was demonstrated in both serum and plasma. Moreover, using a specific semiquantitative dot-blot system, we found CD89 in all human sera tested (mean concentration 1900 ng/ml). Size fractionation of human serum using gel filtration chromatography showed that the CD89 molecule was predominantly present in larger molecular mass fractions. Direct complexes between IgA and CD89 were demonstrated by anti-IgA affinity purification, and when analyzed under nonreducing conditions appeared to be covalently linked. Size fractionation of affinity-purified IgA showed the presence of soluble CD89 only in the high molecular mass fractions of IgA, but not in monomeric IgA. High molecular mass complexes of CD89-IgA could be distinguished from J chain containing dimeric IgA. These data show that CD89 circulates in complex with IgA, and suggest that CD89 might contribute to the formation of polymeric serum IgA.

show abstract

Section: Iga-cd89 and Iga-j Chain Complexes Can Be Distinguished In Dmentioning

confidence: 99%

FcαRI/CD89 Circulates in Human Serum Covalently Linked to IgA in a Polymeric State

Boog

Zandbergen

Fijter

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…It is often assumed that pIgA and pentameric IgM contain only one J chain molecule (26), but immunochemical studies have suggested that dimeric IgA contains two and pentameric IgM three to four J chains (27,28). Characterization of J chain released from dimeric, trimeric, and tetrameric IgA purified from the same myeloma serum did indeed suggest that the molar J chain ratio increases with the size of the polymer (29).…”

mentioning

confidence: 99%

The J Chain Is Essential for Polymeric Ig Receptor-Mediated Epithelial Transport of IgA

Johansen

Braathen

Brandtzæg

2001

The Journal of Immunology

185

135

View full text Add to dashboard Cite

Local production of secretory (S)IgA provides adaptive immunologic protection of mucosal surfaces, but SIgA is also protective when administered passively, such as in breast milk. Therefore, SIgA is a potential candidate for therapeutic administration, but its complex structure with four different polypeptide chains produced by two distinct cell types complicates recombinant production. The J chain is critical in the structure of SIgA because it is required for efficient polymerization of IgA and for the affinity of such polymers to the secretory component (SC)/polymeric (p)IgR. To better understand the role of the J chain in SIgA production, we have generated various mutant forms of the human J chain and analyzed the function of these mutants when coexpressed with IgA. We found that the C terminus of the J chain was not required for the formation of IgA polymers, but was essential for the binding of pIgA to SC. Likewise, we found that two of the intrachain disulfide bridges (Cys13:Cys101 and Cys109:Cys134) were also required for the binding of pIgA to SC but, interestingly, not for IgA polymerization. Conversely, the last intrachain disulfide bridge (Cys72:Cys92) was not essential for either of these two J chain functions. Finally, we demonstrated that the presence of only Cys15 or Cys69 was sufficient to support polymerization of IgA, but that these polymers were mostly noncovalently stabilized. Nevertheless, these polymers bound free SC with nearly the same affinity as pIgA containing wild-type J chain, but were transcytosed by pIgR-expressing polarized epithelial cells at a reduced efficiency.

show abstract

“…In our present study, pIgA(Gera) contained a J chain, both by SDS-PAGE and Western blot [30]. Moreover, propionic aciddenatured pIgA(Gera), which still contains the J chain ( [19,20] data not shown) was poorly transported into bile, suggesting that the J chain and § chains must be in their native state in pIgA to interact properly with SC/ pIgR. An altered conformation was probably incompatible with a proper SC/pIgR binding site.…”

Section: Discussionmentioning

confidence: 95%

“…4.2), although unable to precipitate native J chain-containing pIgA and IgM, do interact with the native pIg [19,20]. To confirm such interaction using anti-J(K) IgG, a fixed amount of 125 I-labeled pIgA (5 ?…”

Section: Interaction Of Anti-j(k) Igg With Human 125 Ilabeled Pigamentioning

confidence: 92%

“…Occasionally, IgM and pIgA, which have a very low J chain content, have been shown to interact with SC/ pIgR to a much lesser extent [16,17], with some exceptions [18]. Antibodies against purified J chain precipitate isolated free J chain, and bind in vitro to native J chain- containing pIg without precipitation [19,20]. Such binding decreased the interaction between FSC and pIg [21].…”

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

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

et al. 1998

View full text Add to dashboard Cite

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.

show abstract

Immunochemical Studies on Free and Bound J Chain of Human IgA and IgM

Cited by 50 publications

References 29 publications

FcαRI/CD89 Circulates in Human Serum Covalently Linked to IgA in a Polymeric State

FcαRI/CD89 Circulates in Human Serum Covalently Linked to IgA in a Polymeric State

The J Chain Is Essential for Polymeric Ig Receptor-Mediated Epithelial Transport of IgA

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

Contact Info

Product

Resources

About