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Genes predisposing to autoimmunity augment constitutive major histocompatibility complex class II‐associated presentation of the self‐antigen IgG2a b in vivo
Author(s) -
Bartnes K.,
Li X.,
Iwamoto M.,
Izui S.,
Hannestad K.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00062.x
Subject(s) - antigen presentation , immunology , biology , antigen , autoimmunity , major histocompatibility complex , systemic lupus erythematosus , b cell , immune system , t cell , antibody , medicine , disease
Summary The self‐antigen IgG2a b is poorly presented to a γ2a b 435–451‐reactive I‐A d ‐restricted T‐cell hybridoma unless available in high concentrations or targeted to Fcγ‐ or complement receptors. Environmental factors, probably the extent of microbial challenge, profoundly influence the constitutive γ2a b /I‐A d presentation in IgC H b , H‐2 d mice. Here we report also a strong genetic impact. Constitutive presentation was highly efficient in spleen and thymus of (NZB × BXSB)F 1 mice, which inherit a predisposition to develop lupus. Presentation correlated with disease progression and the serum levels of IgG2a b and IgG2a b complement factor 3 complexes. The finding that constitutive presentation was by far most efficient in males indicated that it was augmented by the Y chromosome‐linked autoimmune acceleration Yaa gene. In line with previous data for healthy mice, constitutive γ2a b /I‐A d presentation was most pronounced in the adherent spleen cell fraction and improved by further enrichment for dendritic cells. Notably, however, whereas in normal mice the γ2a b determinant was undetectable on B cells lacking surface IgG2a b , such B cells contributed considerably to constitutive presentation in (NZB × BXSB)F 1 hybrids. Presumably this resulted from complement receptor‐mediated internalization of IgG2a b ‐containing immune complexes formed in lupus. These data add to the evidence that B cells with self‐reactive receptors, known to exist in the mature repertoire, may present non‐cognate foreign antigen to anti‐foreign helper T lymphocytes and thus differentiate into autoantibody‐secreting cells, and might likewise account for the polyclonal B‐cell activation characteristic of several autoimmune syndromes.