Lower levels of surface B-cell-receptor expression in chronic lymphocytic leukemia are associated with glycosylation and folding defects of the μ and CD79a chains

Abnormal levels of the α chain of the CD22 adhesion molecule may account for low CD22 surface expression in chronic lymphocytic leukemia

“…These results suggest that in B-CLL cells, despite the presence of a mature b chain, absence or very low level of CD22a chain may account for an incomplete CD22 molecule and may lead to low surface expression. This result is reminiscent of our previous results 5 showing that the CD79b, which is present in a mature glycoform, is very poorly expressed at the cell surface, as a consequence of poor assembly of the BCR components.…”

“…3,4 We reported that underexpression of the BCR in B-CLL cells is associated with glycosylation and folding defects of the m and CD79a chains, but not of the CD79b. 5 We investigated here the defect of CD22 surface expression in B-CLL cells by analyzing CD22a and b chains at the genetic, transcriptional and post-transcriptional level.…”

IL-4 rescues surface IgM expression in chronic lymphocytic leukemia

“…by guest www.bloodjournal.org From CLL cells. 31 We find that IL-4 induces CD79b protein, increases sIgM expression, and upregulates BCR responsiveness to antigen. Antigen binding leads to internalization of BCR complexes that is counterbalanced by IL-4.…”

“…28 The latter is a prerequisite for, and sufficient to promote, maturation and membrane transport of IgM. 29,30 CLL cells exhibit glycosylation and folding defects of the IgM and CD79a chains, 31 which results in impaired BCR assembly and reduced sIgM in CLL samples. Our recent studies [32][33][34] have shown that IL-4 reprograms sIgM expression and substantially enhances anti-Ig-initiated B-cell activation in mouse B cells.…”

Golgi Specificity and Development of Autoreactive B Cells

“…These cells however, secrete incompletely assembled 7S IgM (258). In chronic lymphocytic leukemias of B cells (B-CLLs), impaired glycosylation and misfolded μ Hc lead to retention of IgM in the ER and nascent IgM remains unsuitable for secretion (280). Nevertheless, the production of spherons appears to be a surprisingly efficient way to extrude IgM aggregates from the cell.…”