Role of the fourth complement component (C4) in the regulation of contact sensitivity. I. Analysis in mice with high and low C4 levels.

Lymph node cells collected from CBA/J mice 4 days after painting the skin with picryl chloride are able to immunize naive recipients by hapten-IgM immuno complexes. These cells ("4-day" cells) activate the early components of the classical pathway of complement from mice of the H-2 Sd haplotype (high-C4), but fail to activate the classical pathway of complement from mice of the H-2 Sk haplotype (low-C4). Incubation of "4-day" cells in complement from mice with high-C4 levels abolishes the induction of contact sensitivity, probably as a consequence of the solubilization of membrane-bound immuno complexes caused by complement activation. The presence of "4-day" cells is determined by the levels of C4. In fact, using strains of mice which differ only at the S region of the H-2 complex, we found that mice of the H-2 Sd (and perhaps H-2 Sb) haplotype (high-C4 levels) lack "4-day" cells in their lymph nodes and this is due to the activation of the early components of the classical complement pathway which occurs in vivo in these mice during sensitization with picryl chloride. The finding that contact sensitivity reaction to picryl chloride in H-2 Sk mice lasts about 21 days, whereas H-2 Sd mice show a contact sensitivity reaction until 7 days after sensitization, strongly suggests that the S region, and in particular C4 levels, controls the persistence of "4-day" immunogenic cells, and so play a role in the duration of the contact sensitivity reaction to picryl chloride in the mouse.