Possible allelic structure of IgG2a and IgG2c in mice (1)
Igh-1a and Igh-1b could derive from two distinct isotypes, IgG2a and IgG2c, which are organized in tandem on the same chromosome as two distinct loci in MAI strain and BALB/c and C57B/6 mice carry different IgG2a isotypes. Expression of only IgG2c in C57B/6 and SJL mice was discovered and was assumed to be caused by a deletion of IgG2a gene in those strains. Some mice have single copies of the IgG2a or IgG2c gene on individual alleles.
In total, 64 mice were collected for sequence analysis, including 28 APP/PS1 transgenic mice and 36 mice from five different strains of mice (4 C57B/6, 4 NMRI, 4 SJL, 4 DBA/2 and 20 Swiss Webster from Taconic). Sequencing data showed thatthe IgG2a gene is highly polymorphic between the NMRI, DBA/2 and Swiss Webster strains. No coding polymorphism within the IgG2c gene was identified in all our analyzed mice.
Only the IgG2a gene was found in DBA2 and NMRI strains while the IgG2c gene was present in C57B/6 and SJL strains. Both IgG2a and IgG2c were found to be present in Swiss Webster and APP/PS1 transgenic mice. IgG2a and IgG2c are not physically linked on the chromosome and are allelic-single locus. IgG2b–IgG2a and IgG2b–IgG2c are likely to be most common haplotypes (physical position) in mice. Divergences of protein sequence between IgG2a and IgG2c (15% in protein sequence) indicated that IgG2a and IgG2c likely have different immune profile in mice.
Mice lacking IgG2a could theoretically lack tolerance to IgG2a and mount an immune response to injected IgG2a antibodies, neutralize and increase plasma clearance, which will interfere with the conclusion of study. Inbred mice, such as C57B/6, NMRI, SJL and DBA/2 strains, produce different IgG2a isotypes; C57B/6 and SJL mice secrete IgG2c while NMRI and DBA/2 mice
secrete IgG2a. The situation becomes more complicated for Swiss Webster mice (outbred); mice may secrete only IgG2a, or IgG2c, or both IgG2a and IgG2c.