Antigen-specific versus total immunoglobulin synthesis: total IgE and IgG1, but not IgG2a levels predict murine antigen-specific responses.
BACKGROUND
Induction of an effective antibody (Ab) response requires delivery of multiple signals to B cells. Cross-linking of the B cell antigen receptor (BCR), signaling through CD40 and CD80/86 and cytokine signals combine to induce class switching and expression of specific isotypes. These signals are principally derived from activated, antigen (Ag)-specific T cells. In contrast, IFNgamma, the only cytokine known to induce class switch to IgG2a, can be produced systemically by activated NK or NKT cells, suggesting that Ag-nonspecific signals may also regulate IgG2a production.


METHODS
Given the potential differences in regulation between IgE/IgG1 versus IgG2a, we immunized mice on day 0 with ovalbumin (OVA) in the presence of strong type-1- or type-2-immunity-inducing adjuvants and boosted mice 4 weeks later. Mice were bled during the primary immune response and after boost to assess primary and recall Ab responses.


RESULTS
Regardless of strain of mice used, phenotype (type 1 versus type 2 dominated) or nature of the immune response induced (primary versus recall), strong correlations between OVA-specific and total IgE and IgG1 were demonstrated. In contrast, a consistent lack of correlation between OVA-specific and total IgG2a levels was observed in all but BALB/c mice.


CONCLUSIONS
These data indicate that the increase in total levels of IgE/IgG1 isotypes is primarily a result of increased levels of OVA-specific Ab. In contrast, the lack of correlation between total and OVA-specific IgG2a suggests broader activation of IgG2a-producing B cells routinely occurs following exogenous Ag immunization.
Lewkowich
Ian P
IP
Department of Immunology, CIHR National Training Program in Allergy and Asthma Research, Winnipeg, Canada.
Rempel
Julia D
JD
HayGlass
Kent T
KT
D000276:Adjuvants, Immunologic; D000818:Animals; D000939:Epitopes / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000939:Epitopes; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin