Increased Utilization of Polyreactive B Cells During Periods of Generalized Immune Activation

Abstract

This work examines the hypothesis that B cells secreting polyreactive antibodies (antibodies capable of binding to more than one self or foreign antigen) are preferentially utilized during periods of generalized immune stimulation. Four conditions characterized by such stimulation were examined: chronic virus infection, mitogen treatment, autoimmune disease and neonatal repertoire development. In normal adult mice, polyreactive IgM secreting lymphocytes constituted 8–9% of the actively expressed repertoire. Under conditions of generalized immune activation, this frequency increased to 13–19% (p. <. 01). Polyreactive IgG secreting B cells, which were present at frequencies of < 0.5% in normal adult mice, were found at freqeuncies of 6–10% in mice with autoimmune disease, chronic virus infection or following mitogen treatment (p. <. 001). We postulate that polyreactive lymphocytes are preferentially activated when the immune system is confronted with stimuli inadequately controlled by antigen-specific responses.

Key Words:

• B cells
• cross-reactivity
• polyreactivity
• repertoire
• autoimmunity