Differential Susceptibility of Human IgA Immunoglobulins to Streptococcal IgA Protease

Plaut, Andrew G.; Wistar, Richard; Capra, J. Donald

doi:10.1172/jci107875

Cited by 100 publications

(47 citation statements)

References 16 publications

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“…27 ). This feature renders IgA1 more susceptible to degradation by bacterial proteases that target the hinge region of IgA 23,28 . Furthermore, compared to IgA1 antibodies, IgA2 antibodies seem to have superior Fcα-mediated, mannose-dependent agglutinating properties against enteric microorganisms and exhibit more V H -mediated reactivity against LPS, a key component of Gram-negative bacteria residing in the distal gut 23,25 .…”

Section: Human Iga Subclassesmentioning

confidence: 99%

“…Together with IL-10, APRIL triggers IgA2 CSR in B cells 26 , suggesting that epithelial cells are central to the induction of IgA2 at mucosal sites colonized by a large microbiota, such as the colon 24,25 . At these sites, IgA2 may be more beneficial than IgA1, perhaps because IgA2 is more resistant than IgA1 to enzymatic digestion by bacterial proteases 25,28 .…”

Section: Role Of Epithelial Cells In Csr To C αmentioning

confidence: 99%

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The regulation of IgA class switching

2008

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IgA class switching is the process whereby B cells acquire the expression of IgA, the most abundant antibody isotype in mucosal secretions. IgA class switching occurs via both T-celldependent and T-cell-independent pathways, and the antibody targets both pathogenic and commensal microorganisms. This Review describes recent advances indicating that innate immune recognition of microbial signatures at the epithelial-cell barrier is central to the selective induction of mucosal IgA class switching. In addition, the mechanisms of IgA class switching at follicular and extrafollicular sites within the mucosal environment are summarized. A better understanding of these mechanisms may help in the development of more effective mucosal vaccines.IgA has been selected throughout evolution to provide a first line of immune protection at mucosal surfaces -vulnerable frontline sites that are exposed to potentially harmful commensal, airborne, ingested and sexually transmitted agents. Growing evidence indicates that IgA uses a high-affinity binding system to neutralize microbial toxins and pathogens, and a low-affinity binding system to prevent commensal bacteria from breaching the mucosal surface 1 . This latter process is known as immune exclusion and has a fundamental role in the intestine, which is home to a number of commensal bacteria exceeding that of human cells by an estimated order of magnitude 2 .Remarkably, intestinal IgA achieves both immune protection and immune exclusion in a non-inflammatory manner, thereby promoting the establishment of a sustainable hostmicrobial mutualism 3 . The complex relationship between IgA and the intestinal microbiota is further exemplified by the fact that IgA responses are highly dependent on intestinal colonization by commensal microorganisms. Indeed, the number of IgA-secreting B cells is dramatically reduced in the intestine of germ-free animals and these cells are virtually absent in neonates before their exposure to bacteria 3 .In this Review, I summarize recent advances in our understanding of the function, regulation and geography of IgA class switching. In addition to analysing the signalling pathways underlying IgA class switching, I discuss new evidence indicating that commensal bacteria Competing interests statementThe author declares no competing financial interests. DATABASES Function of IgA class switchingAntibody diversification is essential for the immune system to mount protective humoral responses. B cells diversify their antibody repertoire through three main genetic alterations that occur in two distinct phases of B-cell development. In the antigen-independent phase, B-cell precursors lodged in the bone marrow generate antigen recognition diversity by assembling the exons that encode immunoglobulin heavy (H) and light (L) chain variable regions from individual variable (V), diversity (D) and joining (J) gene segments through V(D)J gene recombination 4 . This process is initiated by a lymphoid-cell-and sequencespecific RAG1 (recombination-activating gene 1...

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Section: Human Iga Subclassesmentioning

confidence: 99%

Section: Role Of Epithelial Cells In Csr To C αmentioning

confidence: 99%

The regulation of IgA class switching

2008

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“…IgA appears to be involved in several defense mechanisms, including the inhibition of microbial adherence and the neutralization of bacterial toxins and viruses. At the beginning of the 1970s, Plaut and coworkers found that IgA is degraded by some bacterial enzymes (323,(396)(397)(398)(399)(400). Later, this event was implicated as an evasion mechanism of immune responses (398).…”

Section: Iga1 Proteasesmentioning

confidence: 99%

Type V Protein Secretion Pathway: the Autotransporter Story

Henderson

Navarro-Garcı́a

Desvaux

et al. 2004

Microbiol Mol Biol Rev

713

795

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Gram-negative bacteria possess an outer membrane layer which constrains uptake and secretion of solutes and polypeptides. To overcome this barrier, bacteria have developed several systems for protein secretion. The type V secretion pathway encompasses the autotransporter proteins, the two-partner secretion system, and the recently described type Vc or AT-2 family of proteins. Since its discovery in the late 1980s, this family of secreted proteins has expanded continuously, due largely to the advent of the genomic age, to become the largest group of secreted proteins in gram-negative bacteria. Several of these proteins play essential roles in the pathogenesis of bacterial infections and have been characterized in detail, demonstrating a diverse array of function including the ability to condense host cell actin and to modulate apoptosis. However, most of the autotransporter proteins remain to be characterized. In light of new discoveries and controversies in this research field, this review considers the autotransporter secretion process in the context of the more general field of bacterial protein translocation and exoprotein function

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“…As a result of this specific IgA-protease activity, the IgA molecule is cleaved into a stable Fc fragment and two monomeric Fab fragments that retain their antigenbinding capacity (73,74). IgA2 is more resistant to proteolysis due to the lack of a specific peptide stretch that can be found in the hinge region of IgA1 (87). These IgA-proteases have been shown to inactivate IgA by cleaving in the hinge region (86), but their importance as virulence determinants has been debated.…”

Section: Microbial Immunoglobulin Proteasesmentioning

confidence: 99%