Immunologic basis for the rare occurrence of true nonsecretory plasma cell dyscrasias

Catherine Decourt , Horia Radu Galea , Christophe Sirac , and Michel Cogné ^@

CNRS UMR 6101, Laboratory of Immunology, Faculté de Médecine et Hôpital Universitaire Dupuytren, Limoges, France

^@ To whom correspondence should be addressed. E-mail: cogne{at}unilim.fr.

Abstract

Lymphocytes and plasma cells are major actors of the adaptiveimmune response and can rightly be considered as human healthkeepers. However, recombination and mutation events occurringat high rate in the B cell lineage also expose these cells togene alterations, potentially resulting in uncontrolled andlife-threatening cell proliferation. Although in cultured celllines, such gene alterations frequently generate nonsecretoryvariants, most immunoproliferative B cell disorders featurein vivo immunoglobulin (Ig) secretion. In this paper, we reviewthe molecular mechanisms involved in various instances of therare, nonsecretory myelomas, in light of current notions aboutthe molecular control of Ig production, assembly, and secretionin normal B cells. We finally document the attractive hypothesisthat B cell clones, which retain nonsecretable, intracellularIgs, may be ideal, in vivo targets for efficient anti-idiotypicimmune responses, and clones featuring an abundant secretionmay by contrast easily induce T cell anergy and escape the anti-tumoralimmune surveillance.

Key Words: immunoproliferative • B cells • immunoglobulin secretion • myeloma

Article

Immunologic basis for the rare occurrence of true nonsecretory plasma cell dyscrasias