Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces.

Hamadeh, R M; Jarvis, Gary A.; Galili, Uri; Mandrell, Robert E.; Zhou, Ping; Griffiss, J. McLeod

doi:10.1172/jci115706

Cited by 119 publications

(97 citation statements)

References 46 publications

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“…In humans, ␣Gal-specific Abs are encoded for by a restricted set of Ig Vh genes from the V H 3 family (14). Production of Abs specific for ␣Gal is believed to be elicited in response to normal bacterial flora that colonize the human gastrointestinal tract (11,15). The presence of anti-␣Gal Ab in serum and secretory fluids, such as colostrum and saliva, suggests that these Abs have evolved to play a protective role in primate immunity.…”

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confidence: 99%

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Benatuil

Kaye

Crétin

et al. 2008

The Journal of Immunology

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Natural Abs specific for the carbohydrate Ag Galα1–3Galβ1–4GlcNAc-R (αGal) play an important role in providing protective host immunity to various pathogens; yet little is known about how production of these or other anti-carbohydrate natural Abs is regulated. In this study, we describe the generation of Ig knock-in mice carrying functionally rearranged H chain and L chain variable region genes isolated from a B cell hybridoma producing αGal-specific IgM Ab that make it possible to examine the development of B cells producing anti-carbohydrate natural Abs in the presence or absence of αGal as a self-Ag. Knock-in mice on a αGal-deficient background spontaneously developed αGal-specific IgM Abs of a sufficiently high titer to mediate rejection of αGal expressing cardiac transplants. In the spleen of these mice, B cells expressing αGal-specific IgM are located in the marginal zone. In knock-in mice that express αGal, B cells expressing the knocked in BCR undergo negative selection via receptor editing. Interestingly, production of low affinity αGal-specific Ab was observed in mice that express αGal that carry two copies of the knocked in H chain. We suggest that in these mice, receptor editing functioned to lower the affinity for self-Ag below a threshold that would result in overt pathology, while allowing development of low affinity anti-self Abs.

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confidence: 99%

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Benatuil

Kaye

Crétin

et al. 2008

The Journal of Immunology

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“…Production of natural Abs specific for ␣Gal is thought to occur following exposure to bacteria that colonize the gastrointestinal tract (7,8). The presence of these Abs in serum and secretory fluids, such as colostrum and saliva, suggests that these Abs have evolved to play a protective role in primate immunity.…”

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confidence: 99%

The Role of T Cell Help in the Production of Antibodies Specific for Galα1–3Gal

Crétin

Bracy

Hanson

et al. 2002

The Journal of Immunology

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The majority of xenoreactive natural Abs in humans recognize the carbohydrate Ag present on pig tissue, Galα1–3Galβ1–4GlcNAc-R (αGal), synthesized by the enzyme UDP galactose:β-d-galactosyl-1,4-N-acetyl-d-glucosaminide α(1–3)galactosyltransferase or αGT. Using αGT knockout mice (GT0 mice), which like humans produce serum Abs that bind αGal, we examined the role of T cells in production of Abs specific for αGal. GT0 mice were crossed with TCR-β knockout mice (TCR-β0) to generate double-knockout mice (GT0/TCR-β0). While GT0/TCR-β+ mice exhibited an age-dependent increase in the serum titer of natural Abs specific for αGal, a similar increase was not observed in GT0/TCR-β0 mice, and the titer of αGal-specific Abs in double knockouts was significantly lower than in age-matched GT0/TCR-β+ mice. Immunization with pig cells resulted in a significant increase in the serum titer of αGal-specific Abs in GT0/TCR-β+ mice, but had no effect on the level of αGal-specific serum Abs in GT0/TCR-β0 mice. Treatment of GT0/TCR-β+ mice with anti-CD40L Abs before immunization with pig cells prevented sensitization to αGal. Our data suggest that the majority of αGal-specific Abs are T cell dependent and that production of αGal-specific Abs after sensitization can be prevented by blocking costimulatory pathways.

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“…While the linkage region between PS-2 and peptidoglycan has not been identified yet, PS-2 as well as many other bacterial cell wall polymers is presumed to link to the muramic acid 6-phosphate of peptidoglycan through a phosphodiester linkage, because the purified cell walls contained only glucose, galactose, and peptidoglycan components, except for a slight level of fatty acid. Recently, human natural antigalactosyl antibody has been reported to interact with some bacteria isolated from human flora (6,8). We have found that B. infantis cell walls activate the alternative pathway of human complement system and that this ability of the cell walls is abolished by removing the polysaccharides (unpublished experiments), suggesting that the cell wall polysaccharides react with the antibody.…”

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confidence: 71%

Isolation and structural analysis of polysaccharide containing galactofuranose from the cell walls of Bifidobacterium infantis

1996

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We isolated cell wall polysaccharides (PS-1 and PS-2) from Bifidobacterium infantisBifidobacteria are anaerobic gram-positive bacteria and are believed to be associated with health-promoting effects in the host intestine. Recent studies with several Bifidobacterium strains have offered structural information concerning the cell surface construction, such as lipoteichoic acids (4,5,10,18), teichoic acids (26), and cell wall polysaccharides (7,17). Op den Camp et al. have isolated from Bifidobacterium bifidum a new type of lipoteichoic acid, containing a 1,2-linked polyglycerophosphate backbone between a glycolipid moiety and a linear polysaccharide, and found a unique structure, 1,5-linked ␤-D-galactofuranose homopolymer (galactofuranan), in the polysaccharide chain (18). On the other hand, Fischer et al. have provided another structure for lipoteichoic acid-like amphipathic polymers, which consist of a glycolipid moiety, 1,6-linked ␤-glucan, and 1,5-linked ␤-galactofuranan with side chains of monomeric glycerophosphate (4, 5). Such macroamphiphiles do not link to peptidoglycan but are considered to be anchored to membranes through their lipid moiety and should be common in several species of Bifidobacterium (10).Previously, we reported the carbohydrate composition of purified cell walls of Bifidobacterium infantis Reuter ATCC 15697 (24). In the present study, we isolated two distinct neutral polysaccharides, PS-1 and PS-2, from the purified cell walls of the same strain and found that the backbone of PS-2 is a 1,3-linked galactan consisting of ␤-D-galactofuranose and ␣-Dgalactopyranose in which more than 90% of the ␤-D-galactofuranosyl residues and about 30% of ␣-D-galactopyranosyl residues are occupied by ␤-D-glucopyranose at position 6. The backbone structure, 33)-␤-D-Gal f -(133)-␣-D-Gal p -(13, has been identified also in the lipopolysaccharide of Klebsiella pneumoniae (12-15, 27, 28), Pasteurella haemolytica (22, 23), Serratia marcescens (19,20), and Serratia plymuthica (1). It is of interest that the cell wall polysaccharide from B. infantis contains the same structure as O-specific antigen of some gramnegative bacteria.Preparation and carbohydrate composition of cell wall polysaccharides, PS-1 and PS-2. We previously described the growth conditions of B. infantis and the isolation procedure of purified cell walls (24). Determinations of amino acids, monosaccharides, fatty acids, and nucleic acids of the cell walls were also carried out by the same methods as previously reported (24). B. infantis cell walls consisted of neutral sugars (glucose and galactose), amino sugars (glucosamine and muramic acid), peptidoglycan-derived amino acids (alanine, glutamic acid, threonine, serine, and ornithine), and a small amount of fatty acids, so that they were considered to be free from contamination with nucleic acids and proteins (24).The purified cell walls (300 mg) were treated with 5% trichloroacetic acid at 4ЊC overnight and then centrifuged, and the supernatant was thoroughly dialyzed against deionized water. T...

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Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces.

Cited by 119 publications

References 46 publications

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

Ig Knock-In Mice Producing Anti-Carbohydrate Antibodies: Breakthrough of B Cells Producing Low Affinity Anti-Self Antibodies

The Role of T Cell Help in the Production of Antibodies Specific for Galα1–3Gal

Isolation and structural analysis of polysaccharide containing galactofuranose from the cell walls of Bifidobacterium infantis

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