Reversible anergy of sIgM-mediated signaling in the two subsets of CLL defined by VH-gene mutational status.

The 2 subsets of chronic lymphocytic leukemia (CLL), of worse or better prognosis, likely derive from pre-GC unmutated B cells, or post-GC mutated B cells, respectively. Different clinical behavior could relate to the ability of tumor cells to respond to surface (sIg)-mediated signals. Unmutated cases (U-CLL) have an increased ability to phosphorylate p72(Syk) in response to sIgM ligation compared to mutated cases (M-CLL).

Structural and functional features of the B-cell receptor in IgG-positive chronic lymphocytic leukemia.

Purpose: To determine the origin and relationship of the rare IgG+ variant of chronic lymphocytic leukemia (CLL) to the two common IgM+IgD+ subsets that are distinguished by expression of unmutated or mutated V(H) genes, with the former having a worse prognosis.

Experimental Design: IgG+ CLL cells were characterized using phenotypic, functional, and immunogenetic analyses.

Results: IgG+ CLL was phenotypically similar to mutated IgM+IgD+ CLL (M-CLL) and variably expressed CD38 (4 of 14).