The nature and origin of the B-chronic lymphocytic leukemia cell: a tentative model

Chronic lymphocytic leukemia cells have the profile of antigen (Ag) activated memory B cells but also show a constellation of T-cell-associated properties. We suggest that the early transforming events may occur in an early lymphoid progenitor. This precursor differentiates into a mature B cell that, though retaining T-cell features, has a functional B-cell receptor that may allow Ag intervention to trigger clonal expansion. This model has to cope with the existence of at least two subsets of the disease as defined by their IgVH genes mutational status. Mutated cases have a lower capacity to interact with Ag and are reminiscent of anergic cells. This explains their less harmful behavior as compared with unmutated case, which have a more aggressive potential likely because they had the opportunity to acquire additional chromosomal aberrations after repeated rounds of Ag stimulation and replication.