Abstract
Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease. Immunophenotypic and molecular approaches (including immunoglobulin heavy-chain variable gene mutational status, transcriptional and epigenetic profiling) comparing the normal B-cell subset and CLL B-cells provide some new insights into the normal cellular counterpart. Functional characteristics (including activation requirements and propensity for plasma cell differentiation) of CLL B-cells have now been investigated for 50 years. B-cell subsets differ substantially in terms of their functional features. Analysis of shared functional characteristics may reveal similarities between normal B-cell subsets and CLL B-cells, allowing speculative assignment of a normal cellular counterpart for CLL B-cells. In this review, we summarize current data regarding peripheral B-cell differentiation and human B-cell subsets and suggest possibilities for a normal cellular counterpart based on the functional characteristics of CLL B-cells. However, a definitive normal cellular counterpart cannot be attributed on the basis of the available data. We discuss the functional characteristics required for a cell to be logically considered to be the normal counterpart of CLL B-cells.
Highlights
B-cell chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and accumulation of mature CD5+ B lymphocytes in bone marrow, peripheral blood, and lymphoid tissues [1, 2]
In all studies investigating differentiation of Chronic lymphocytic leukemia (CLL) B-cells into antibody-secreting plasma cells (ASPCs), CLL B-cells show a high propensity for differentiation into plasma cell (PC) that predominantly secrete IgM (Figure 3)
These data indicate that CLL B-cells originate from a B-cell compartment that rapidly differentiates into predominantly IgM-producing ASPCs with little isotype switching
Summary
B-cell chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and accumulation of mature CD5+ B lymphocytes in bone marrow, peripheral blood, and lymphoid tissues [1, 2]. IgM MBC share several functions and phenotypic characteristics with human B1-like cells, MZB-cells, and mouse B1a cells [49, 60,61,62]; they are thought to be the major source of “natural” Abs in the body, can express Igs with low-frequency somatic hypermutation (SHM) and produce IgM (and some IgG and IgA, after in vitro differentiation) [60, 61].
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