Intact B cell tolerance in the absence of the first component of the classical complement pathway

A critical role for complement in the regulation of self tolerance has been proposed to explain the strong association between complement deficiency a nd autoimmunity. To elucidate the role of the classical pathway of compleme nt in the maintenance of B cell tolerance, Clq deficient (C1qa-/-) mice wer e bred with anti-hen egg lysozyme (MEL) immunoglobulin (Ig(HEL)) and solubl e MEL (sHEL) transgenic mice. B cell tolerance was intact in C1qa-/- mice. In vivo, double-transgenic (Ig(HEL)/sHEL) C1qa-/- and wild-type control mic e down-regulated surface immunoglobulin expression on splenocytes and equiv alent numbers of MEL-binding B cells accumulated in the periphery. Maturati on of B cells, evidenced by CD21 expression, was retarded to the same exten t and at a similar time point. The frequency of anti-MEL-producing plasma c ells and serum levels of anti-MEL immunoglobulin were comparably reduced in control and C1qa-/- double-transgenic mice compared to control Ig(HEL) and C1qa-/- Ig(HEL) mice. Furthermore, splenocytes from double-transgenic C1qa -/- or wild-type mice did not modulate intracellular calcium levels after s timulation with MEL in vitro. These data demonstrate that a stable form of B cell anergy persists in the periphery of C1qa-/- mice, suggesting that ac tivation of the classical pathway by C1q is not essential for the maintenan ce of B cell tolerance in this transgenic model.