BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity (1)
IgAs bind to microbial components and affect the invasive potential of microorganisms by inhibiting their interaction with epithelial cells and their subsequent internalization.
BALB/c mice had much higher concentrations of total IgA in both serum and feces compared to C57BL/6 mice. BALB/c mice also had a higher percentage and/or number of B1a B cells both in the spleen and PPs as compared to C57BL/6 mice. BALB/c mice also had a much higher percentage of CD4+ T cells with a T follicular helper cell phenotype (CXCR5+ICOS+) in their PPs, which could indicate also a contribution of T-cell-dependent IgA induction.
Naive BALB/c mice were more protected than C57BL/6 mice in response to Salmonella infection. Naive BALB/c mice had much higher amounts of innate IgA antibodies that could bind to Salmonella both in serum and feces than naive C57BL/6 mice and that might inhibit Salmonella invasive potential. S. Typhimurium aroA induced similar concentration of Salmonella-specific IgA in the feces of C57BL/6 mice and BALB/c mice, but it induced much less Salmonella-specific IgA in the serum of BALB/c mice compared to C57BL/6 mice. After three oral immunizations on alternate days, S. Typhimurium aroAinvA was able to induce Salmonella-specific IgA in the feces of BALB/c but not of C57BL/6 mice. All immunized BALB/c mice survived, but about 60% of immunized C57BL/6 mice did not survive the infection, suggesting that although mice had a similar IgG amounts, only IgAs confer full protection.
Mice that received IgA-coated non-invasive Salmonella had much more bacteria in their PPs but less in the mLNs compared to mice that received non-invasive Salmonella. Higher HEL-specific IgA in the serum of mice that received both bacteria compared to mice that received only the invasive or only the non-invasive strains. Only BALB/c mice were capable of inducing an OVA-specific IgA response both in the feces and blood in response to E. coli OVA administration.
C57BL/6 and BALB/c mice were co-housed for 1 month and polyreactive and total IgA were measured in serum and feces. There was a slight reduction in polyreactive IgA in the serum and feces of co-housed BALB/c mice compared to BALB/c mice that were not co-housed. However, co-housing had no effect on total IgA amounts.
The large majority of identified bacterial species belonged to the phyla Firmicutes and Bacteroidetes for both mice. Co-housing did not affect this difference. BALB/c mice had more diverse microbial communities than C57BL/6 mice as attested by the Shannon diversity index at species level. Co-housing had little effect on diversity but FMT slightly increased diversity in C57BL/6 mice and decreased diversity in BALB/c mice.
BALB/c mice had already a considerable number of innate IgAs in their serum and feces at baseline, suggesting that this was genetically and not microbiota driven. During colonization, the number of IgAs increased in both mouse strains independent of microbiota composition till week 4 in blood and 6 in feces. A situation similar to the one observed during FMT in SPF mice, with BALB/c mice receiving BALB/c inoculum having greater diversity as compared to all the other groups.
Microbiota diversity is genetically and environmentally driven and depends on the amount and diversity of innate IgAs present at birth, which relates to genetic predisposition, lactation, and the type of microbiota that is inherited. There is a memory pool of IgAs that is restored after plasma cell elimination.