Disease relevance of Igh-1b

• Splenocytes from both HSK-susceptible C.AL-20 (Igh-1d) and HSK-resistant C.B-17 (Igh-1b) mice mediated equal amounts of ADCC to HSV-infected cell targets using monoclonal antibodies against HSV-1 glycoprotein D. Natural killer cell activity was significantly greater in C.AL-20 than in C.B-17 splenocytes [1].
• In contrast to NP-induced delayed-type hypersensitivity responses, which only display 4-hydroxy-5-iodo-3-nitrophenyl acetyl (NIP) cross-reactivity in Igh-1b-bearing mice, cross-reactive CS responses can also be elicited in NP-primed mice carrying the Igh-1d, Igh-1e, or Igh-1f allotypes [2].
• Dorf and colleagues (1-4) found that the contact sensitivity (CS) primed with (4-hydroxy-3-nitrophenyl)acetyl (NP) could be elicited as easily with the iodoanalog (NIP) as with NP when studied in Igh-1b mice but could only be elicited with NP, not NIP, in Igh-1j mice [3].
• Clinically observable keratitis began 10 days postinoculation in susceptible C.AL-20 (Igh-1d) and moderately susceptible BALB/c (Igh-1a) mice, whereas HSV-1-resistant C.B-17 (Igh-1b) mice rarely developed disease [4].
• Following intracameral inoculation of 1.5 x 10(4) PFU HSV-1 (KOS), 100% of BALB/c (Igh-1a), 62% of A/J (Igh-1e) and none of the C57BL/6J (Igh-1b) inbred mice developed contralateral necrotizing chorioretinitis [5].

High impact information on Igh-1b

• Treated homozygous Ighb/b mice developed, as of 16-24 wk of age, a chronic suppression of Igh-1b expression (IgG2a of Ighb haplotype) [6].
• In vivo treatment with cytotoxic anti-CD4 or anti-CD8 mAb of mice subjected to chronic Igh-1b suppression clearly showed that CD8+ lymphocytes (suppressor or cytotoxic cell) were essential for the maintenance of the suppression [6].
• This anti-CD8 in vivo treatment was shown to have no effect on thymus but to severely reduce the percentages of CD8+ cells in spleen and in peripheral blood without affecting the percentages of CD4+ cells, leading to a large and rapid Igh-1b expression (up to 0.5 mg per ml of serum, the day after the end of the treatment) [6].
• Interestingly enough, total IgA and IgG2a levels also were higher in Igh-1a than in Igh-1b strains [7].
• The alloantiserum was raised in BALB/c (H-2d, Igh-1a) mice hyperimmunized with spleen cells of Igh allotype congenic mice, CB-20 (H-2d, Igh-1b) [8].

Biological context of Igh-1b

• In order to verify whether the gamma 2a-related isotypic genes, namely gamma 2c and gamma 2a, could correspond to those present as alleles in domestic mice (Igh-1b and Igh-1a), a genomic library from Mus m.musculus strain (MAI) was constructed [9].
• In addition, in vivo these monoclonal antibodies modified anti-SRBC antibody production only in Igh-1b allotype-bearing mice [10].
• With the exception of one allotope located in the hinge region of Igh-1b, all other 23 allotopes examined were preserved upon reduction and alkylation of immunoglobulin antigens [11].
• Genetic studies of determinants recognized by these monoclonal antibodies have also suggested that the distinct Ct molecules of TsF and TaF are encoded by two discrete genes linked to the Igh-1b genes, which are located on the right side of the variable genes of Igh on the 12th chromosome [12].
• Abrogation of Igh-1b suppression by in vivo anti-CD8 mAb treatment was achieved in adult Igha/b heterozygotes but with a lower efficiency than in adult Ighb/b homozygotes, all being chronically Igh-1b suppressed [13].

Anatomical context of Igh-1b

• Monoclonal alloantibodies for T cell allotypic determinants were obtained by hybridizing SP-2 tumor cells with BALB/c (H-2d, Igh-1a) spleen cells, which had been repeatedly immunized with Con A-stimulated CB-20 (H-2d, Igh-1b) spleen cells [10].
• Dendritic cells, macrophages, and B cells were purified from the spleens of Igh-1b mice [14].
• They also did not stain a (T,G)-A--L-specific helper T cell line derived from CWB (H-2b, Igh-1b) mice, which differ from C3H.SW mice only in their heavy chain allotypes [15].
• Bone marrow cells and B splenocytes from Igh-1b-suppressed adult Igha/b mice were shown to be able to durably express Igh-1b when transferred into irradiated Igha/a BALB/c hosts whereas whole spleen cells from such donors failed to do it [13].
• Suppression of Igh-1b anti-sheep red blood cell plaque-forming cells was measured as late as 4 wk after the injection of allotype heterozygous (Igha/b) spleen cells, antiserum, and sheep red blood cells [16].

Associations of Igh-1b with chemical compounds

• Analysis of the antibody response to oxazolone has revealed different ratios of IgG2a and IgG2b antibodies in mice carrying the Igh-1b allele and in strains carrying alleles a, c, and e [17].

Regulatory relationships of Igh-1b

• Exposure to either anti-CD8 or anti-CD4 mAb in vitro or in vivo leads to loss of the capacity of Ts to induce Igh-1b allotypic suppression [13].

Other interactions of Igh-1b

• Segregation analysis with 52 recombinant inbred strains confirmed the close linkage of Igh-Gte idiotype with Igh-1b locus [18].
• Homozygous rig-1d animals heterozygous for the BALB/c Rig-2 allele(s) have very low levels of Igh-1b [19].
• The RF bound specifically to the MRL gamma 2 a allotype (Igh-1j) but not to the B6 gamma 2a allotype (Igh-1b) [20].

Analytical, diagnostic and therapeutic context of Igh-1b

• An indirect asymmetrical sandwich ELISA using anti-allotype antibodies for the specific and quantitative measurement of mouse IgG2a of Igh-1b allotype [21].
• The synthesis and clonal diversity of IgG2a molecules bearing the paternally inherited immunoglobulin allotype have been examined in the offspring of matings between BALB/c mothers (Igh-1a) and SJL or C57BL/10 males (both Igh-1b) using a sensitive quantitative single radial immunodiffusion in gel assay and isoelectric focusing with autoradiography [22].

References