Identification of early plasma cells in peripheral blood and their clinical significance

Abstract

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.

Flow cytometric analysis of normal and reactive spleen

“…Furthermore, CD19 þ CD20À cells expressed high levels of CD38, and were negative for CD138. These results are consistent with the presence in the spleen of a sizable population of early plasma cells, [19][20][21] carrying the CD45 þ CD19 þ CD38 bright, Kappa dim/ negative, Lambda dim/negative, CD20-CD138-phenotype, and accounting for about 6 and 3% of B cells in normal and reactive spleen, respectively. FMC7 antibody has been shown to recognize a CD20-related epitope, presumably derived from a multimeric CD20 complex.…”

“…These results are consistent with the phenotype of early plasma cells. [19][20][21] To compare the frequency of CD19 þ CD20À B cells from human spleen and that from normal peripheral blood or lymph nodes, 11 samples of blood and 8 lymph nodes were analyzed by threecolor flow cytometry for expression of CD45, CD20, and CD19. The frequency of CD19 þ CD20À B cells was lower than 1% in peripheral blood and reached a mean of 1% in lymph nodes (Figure 4b).…”

CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro

“…The frequencies of CD19 + cells and CD27 + B cells, ranging respectively from 2-15% and 15-48%, were not significantly different from the values obtained with HC cells and similar to those previously reported for healthy individuals (Néron et al 2006). In contrast, the frequency of CD138 + cells, ranging from 1.4-10%, was well above normal ranges (p<0.002) compared with HC (0.5±0.4%), which were close to the expected normal frequency of 0.5% (Harada et al 1996). These CD138 + cells expressed CD27 at intermediate levels (mean fluorescence intensity, MFI: 35±15) and a fraction of the cells (6-43%) maintained CD19 expression, indicating that the cells were in transition toward final differentiation.…”

“…High frequencies of CD27 + , CD38 ++ , and CD138 + cells are observed in patient blood showing highly active SLE disease (Harada et al 1996;Odendahl et al 2000;Sato et al 2004). In this study, the disease severity of most of the SLE participants was moderate (SLEDAI ≤9), with only a few cases reaching a level of 12.…”

“…Homeostasis within peripheral B cells from SLE patients is disturbed and can be characterized by an increased frequency of CD27 + cells (Odendahl et al 2000;Jacobi et al 2003). SLE patients with active disease have a higher frequency of circulating blood plasma cells (Harada et al 1996;Jacobi et al 2003). Aberrant levels of soluble or surface molecules involved in B-cell activation, such as interleukin (IL)-10, BAFF, CD40, and CD154 (Gonzalez-Amaro et al 1998;Sun et al 2000;Zouali 2005), as well as enhanced calcium release, defective FcγRIIB signaling, and reduced expression of Lyn [reviewed in (Pugh-Bernard and Cambier 2006)] can all be observed in SLE.…”