The primary IgM antibody repertoire: a source of potent idiotype immunogens

A widely held view is that, to elicit adaptive immune responses, most protein antigens must be given with adjuvants that activate the innate immune system. It has also been proposed that the immune system is tolerant to idiotypes (Id) of the syngeneic primary antibody (Ab) repertoire. We now show that among 73 purified noncomplexed secretory IgM monoclonal antibodies (mAb), 4 (5.5%) elicited high levels of IgG Ab against the Id even though no adjuvant was added. The responses were controlled by H2-linked immune response genes. IgG1, but no IgG2a or IgG2b, anti-Id Ab were detected, indicating involvement of T helper type 2 (Th2) cells. All 4 IgM mAb are likely germ-line gene-encoded, and 1 was shown to represent a recurrent Id. After endotoxin depletion the most potent immunogen of the 4 still provoked robust humoral anti-Id responses. The results suggest that a natural protein of the primary IgM Ab repertoire can be immunogenic without an adjuvant.