Ly-1 B-cell clones similar to human chronic lymphocytic leukemias routinely develop in older normal mice and young autoimmune (New Zealand Black-related) animals.

Abstract

Studies presented here demonstrate that individually expanded clones of murine Ly-1 B cells, perhaps analogous to the expanded neoplastic Leu-1 B-cell clones in human chronic lymphocytic leukemias, are universally detectable in young New Zealand Black (NZB)-related autoimmune mice and in senescent normal mice (>18 months old). These clones are visible as phenotypically homogeneous cell populations in multiparameter fluorescence-activated cell sorter analyses of peritoneal and splenic B cells; they show unique immunoglobulin heavy-and light-chain gene rearrangements in Southern gel analyses of peritoneal and splenic DNA; and, like the self-replenishing Ly-1 B-cell population from which they are drawn, they tend to grow readily in irradiated or unirradiated syngeneic or allotype congenic hosts. Furthermore, they develop and generalize in primary and secondary hosts in a characteristic pattern (peritoneum >> spleen > lymph node > bone marrow) that suggests that their initial growth is controlled by the mechanisms that normally control Ly-1 B-cell distribution in lymphoid organs. The universal emergence of these clones within the Ly-1 B-cell lineage may be explained by the substantially greater opportunity for hyperplastic and neoplastic transformation events in this long-lived self-replenishing Ly-1 B-cell population, which must divide relatively frequently to maintain its normal size throughout adulthood. Repeated exposure to internal or environmental antigens (with which Ly-1 B cells are known to react) may also play a role in driving the development of these clones.Recent studies divide murine B lymphocytes into two lineages: the conventional B-cell lineage, which is replenished from surface immunoglobulin-negative progenitors in the bone marrow; and the Ly-1 B lineage (Ly-1 B), which in the adult is a self-renewing population replenished from immunoglobulin-positive progenitors found largely in the peritoneal cavity (1-3). Ly-1 B cells normally comprise only 1-3% of splenic B cells; however, they constitute 40-80% of the B cells in the peritoneum (1-3). They can express two surface antigens not found on conventional murine B cells, CD5 (Ly-1) (1, 4) and CD11 (MAC-1) (5). In addition, recent studies have shown that within the Ly-1 B-cell lineage two populations exist that can be distinguished by their expression of the CD5 (Ly-1) antigen (ref. 1; A.M.S., unpublished observation). The CD5 + Ly-1 lineage B cells and the CD5 -Ly-1 B cells (also referred to as the sister population) are, except for the expression of the CD5 antigen, phenotypically, developmentally, and functionally indistinguishable. Homologous antigens Leu-1 (CD5) (6) and Leu-15 (CD11) (7) are expressed on human Leu-1 B cells.At the functional level, Ly-1 lineage B cells produce many of the autoantibodies found in normal and New Zealand Black (NZB)-related autoimmune mice (4); in addition, Ly-1

B cells expressing cd5 are increased in sjögren's syndrome

“…Genetically susceptible autoimmune strains of mice also manifest increased numbers of CD5+ B -PHA cells (termed Ly-l), which produce autoantibodies such as anti-erythrocyte and anti-DNA (15). Aged autoimmune mice develop clonal proliferation of Ly-l+ B cells that may be analogous to the B cell lymphomas that arise in humans with primary SS (16,17). In normal mice, Ly-l+ B cells produce growth factors and express helper activity (18).…”

“…Studies in mice demonstrated that a cell analogous to the human CD5-t B cell and expressing cell surface Ly-1 is increased in number in autoimmune mice and becomes clonal in aged mice (15)(16)(17). Recent studies in normal mice suggest that these unusual B cells may have regulatory properties and helper function (18).…”

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Cutting Edge Commentary: Two B-1 or Not To Be One

“…B-1 cells represent the cell of origin for human chronic lymphocytic leukemia, the malignant B cells of which typically express CD5 (40). In mice, monoclonal expansions of B-1 cells that resemble chronic lymphocytic leukemia develop in almost all individuals with increasing age; furthermore, New Zealand Black mice, which contain increased numbers of B-1 cells, develop several types of B-1-derived lymphomatous malignancies early on (41,42). These associations with autoimmune and malignant dyscrasias further impel the drive to understand the regulation of B-1 cell development and activity.…”