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

Lymphocytes and plasma cells are major actors of the adaptive immune response and can rightly be considered as human health keepers. However, recombination and mutation events occurring at high rate in the B cell lineage also expose these cells to gene alterations, potentially resulting in uncontrolled and life-threatening cell proliferation. Although in cultured cell lines, such gene alterations frequently generate nonsecretory variants, most immunoproliferative B cell disorders feature in vivo immunoglobulin (Ig) secretion. In this paper, we review the molecular mechanisms involved in various instances of the rare, nonsecretory myelomas, in light of current notions about the molecular control of Ig production, assembly, and secretion in normal B cells. We finally document the attractive hypothesis that B cell clones, which retain nonsecretable, intracellular Igs, may be ideal, in vivo targets for efficient anti-idiotypic immune responses, and clones featuring an abundant secretion may by contrast easily induce T cell anergy and escape the anti-tumoral immune surveillance.