Detection of immunoglobulin heavy chain IgG3 polymorphism in wild mice with xenogeneic monoclonal antibodies

Huang, Chun-Ming; Huang, Huei-Jen Su; Lee, Sheng-Chung

doi:10.1007/bf00364358

Cited by 9 publications

(4 citation statements)

References 19 publications

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“…Possibly more hybridoma fusions will result in the isolation of MAbs reacting with other OE proteins from L. interrogans. All three MAbs have a kappa-type light chain and none of the MAbs are of the IgG3 subclass, in agreement with the fact that CBA/N mice do not produce immunoglobulins of this subclass (31). Since MAb 1B10H11 has a different isotype, as compared to MAbs 2A8H7 and 6H5G5, at least two hybridomas are different.…”

Section: Discussionsupporting

confidence: 74%

The Use of Immunodeficient Male (CBA/N x BALB/c) F1 Mice to Produce Monoclonal Antibodies Directed to Proteins of Leptospira interrogans Rather than to Immunodominant Lipopolysaccharides

Segers¹,

Nijs²,

Kooten³

et al. 1990

Hybridoma

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A method, using an immunodeficient mouse strain, for the production of monoclonal antibodies directed exclusively against the proteins in an antigen mixture also containing immunodominant LPS, is described. Male (CBA/N x BALB/c) F1 mice were immunized with an outer envelope antigen mixture from Leptospira interrogans strain Wijnberg containing both lipopolysaccharides and proteins. The immune response in these mice was shown to be predominantly directed against protein antigens. Hybridoma cell lines were generated by fusing spleen cells from a (CBA/N x BALB/c) F1 mouse with BALB/c Sp2/0 plasmacytoma cells. Hybridoma cell lines producing monoclonal antibodies reacting with the outer envelope preparation were identified by ELISA. All epitopes recognized by the monoclonal antibodies are sensitive to proteinase K degradation and resistant to oxidation by periodate indicating that they are located on proteins. All epitopes are located on a 35 kDa protein and specific for the pathogenic L. interrogans species.

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Section: Discussionsupporting

confidence: 74%

The Use of Immunodeficient Male (CBA/N x BALB/c) F1 Mice to Produce Monoclonal Antibodies Directed to Proteins of Leptospira interrogans Rather than to Immunodominant Lipopolysaccharides

Segers¹,

Nijs²,

Kooten³

et al. 1990

Hybridoma

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“…The evolutionary or adaptive value for development of enhanced binding by IgG3 is not known. As noted by Greenspan and Cooper [42], the IgG3 C region gene is the most highly conserved of the Ig heavy chain C region genes among inbred mice [43], [44]. Involvement of CH domains in binding (positive or negative effects) may be a general characteristic of antibodies to antigens with repeating subunits such as those in GXM, GlcNAc or γ d PGA.…”

Section: Discussionmentioning

confidence: 95%

IgG Subclass and Heavy Chain Domains Contribute to Binding and Protection by mAbs to the Poly γ-D-glutamic Acid Capsular Antigen of Bacillus anthracis

et al. 2013

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Bacterial capsules are common targets for antibody-mediated immunity. The capsule of Bacillus anthracis is unusual among capsules because it is composed of a polymer of poly-γ-d-glutamic acid (γdPGA). We previously generated murine IgG3 monoclonal antibodies (mAbs) to γdPGA that were protective in a murine model of pulmonary anthrax. IgG3 antibodies are characteristic of the murine response to polysaccharide antigens. The goal of the present study was to produce subclass switch variants of the γdPGA mAbs (IgG3→IgG1→IgG2b→IgG2a) and assess the contribution of subclass to antibody affinity and protection. Subclass switch antibodies had identical variable regions but differed in their heavy chains. The results showed that a switch from the protective IgG3 to IgG1, IgG2b or IgG2a was accompanied by i) a loss of protective activity ii) a change in mAb binding to the capsular matrix, and iii) a loss of affinity. These results identify a role for the heavy chain constant region in mAb binding. Hybrid mAbs were constructed in which the CH1, CH2 or CH3 heavy chain constant domains from a non-protective, low binding IgG2b mAb were swapped into the protective IgG3 mAb. The IgG3 mAb that contained the CH1 domain from IgG2b showed no loss of affinity or protection. In contrast, swapping the CH2 or CH3 domains from IgG2b into IgG3 produced a reduction in affinity and a loss of protection. These studies identify a role for the constant region of IgG heavy chains in affinity and protection against an encapsulated bacterial pathogen.

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“…In mice, the C␥3 gene is thought to be the least polymorphic Ig H chain gene, and it is the only H chain C region locus for which no allotypes have been described in inbred mice (44,45). In humans, IgG2 is thought to have arisen earlier in evolution than the other IgG isotypes.…”

Section: Discussionmentioning

confidence: 99%

Human IgG2 Can Form Covalent Dimers

Yoo

Wims

Chan

et al. 2003

The Journal of Immunology

123

105

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Unlike IgA and IgM, IgG has not yet been shown to form covalent polymers. However in the presence of specific Ag, murine IgG3 has been shown to polymerize through noncovalent interactions. In contrast to the noncovalent oligomers found with murine IgG3, we have detected covalent dimers in three different recombinant human IgG2 Abs produced in myeloma cells. Both IgG2,κ and IgG2,λ can form dimers. In addition, analysis of pooled human γ globulin and several normal sera revealed the presence of IgG2 dimers. The IgG2 dimers are in contrast to the noncovalent IgG dimers found in pooled sera of multiple donors resulting from idiotype/anti-idiotype (Id/anti-Id) interactions. Cyanogen bromide cleavage analysis suggests that one or more Cys residues in the γ2 hinge are involved in dimer assembly. The potential role of IgG2 dimers in immunity against carbohydrate Ags is discussed.

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Detection of immunoglobulin heavy chain IgG3 polymorphism in wild mice with xenogeneic monoclonal antibodies

Cited by 9 publications

References 19 publications

The Use of Immunodeficient Male (CBA/N x BALB/c) F1 Mice to Produce Monoclonal Antibodies Directed to Proteins of Leptospira interrogans Rather than to Immunodominant Lipopolysaccharides

The Use of Immunodeficient Male (CBA/N x BALB/c) F1 Mice to Produce Monoclonal Antibodies Directed to Proteins of Leptospira interrogans Rather than to Immunodominant Lipopolysaccharides

IgG Subclass and Heavy Chain Domains Contribute to Binding and Protection by mAbs to the Poly γ-D-glutamic Acid Capsular Antigen of Bacillus anthracis

Human IgG2 Can Form Covalent Dimers

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