Gaëtan Jégo

Toll-like receptors (TLR) play a central role in the initiation of the innate immune response to pathogens. Upon recognition of molecular motifs specific for microbial molecules TLR mediate pro-inflammatory cytokine secretion and enhance antigen presentation; in B cells they further promote expansion, class switch recombination and immunoglobulin secretion. As a result of their adjuvant properties, TLR ligands have become an integral component of antimicrobial vaccines. In spite of this, little is known of the direct effects of TLR engagement on B-lymphocyte function. The scope of this review is to outline the differences in TLR expression and reactivity in murine and human B-cell subsets and to provide an overview of the currently available literature. We will further discuss the possible roles of TLR in regulating B-cell effector functions and shaping antibody-mediated defence against microbial pathogens in vivo.

The aim of this review is to integrate non-exhaustive relevant data on the phenotype of human plasma cells (PC), including normal, reactive and malignant (multiple myeloma, MM) PC. This review focuses on (i) a universal marker of both normal and malignant plasma cells, CD138; (ii) markers related to malignancy i.e., CD19, CD27, CD28, and CD56; (iii) markers associated with signaling and severity of MM (CD45, CD221). Finally, this review presents data from normal PC up to human myeloma cell lines in order to: (i) define different entities of MM based on expression of CD19, CD20, CD27 and CD117; and (ii) identify new therapeutic targets.

Interleukin-6 (IL-6), although often regarded as a B-cell differentiation factor, was recently described as the essential survival factor for human plasmablasts in vivo in reactive plasmacytosis. The present study reinvestigated the roles of IL-6 and IL-2 in the generation of plasma cells from human memory B cells in vitro. The cells involved in this differentiation process were identified as preplasmablasts (CD20+/-CD38+/-CD138-), plasmablasts (CD20-CD38++CD138-), and early plasma cells (CD20-CD38+++CD138+++). IL-2 or IL-10 induced a strong generation of plasmablasts and early plasma cells (PCs). Compared to IL-2 or IL-10, IL-6 alone was inefficient at PC generation. However, when combined with IL-2 or IL-10, IL-6 enhanced generation of early PCs. Moreover, anti-IL-6 monoclonal antibody markedly reduced IL-2-induced generation of early plasma cells, but not of plasmablasts. These roles of IL-2 and IL-6 were consistent with the difference in the expression of their respective receptors (R). CD25 (IL-2Ralpha) was increased 72 +/- 10-fold on activated B cells, but decreased and then disappeared on plasmablasts. Conversely, CD126 (IL-6Ralpha) was barely expressed on activated B cells, but increased 18 +/- 2-fold on preplasmablasts. Finally, IL-6 enhanced the proliferation (2-fold increase) of IL-2-generated plasmablasts. In conclusion, the data indicate that IL-6 is a growth factor for nonmalignant human plasmablasts.