We have previously described the derivation of M1/70, a hybrid myeloma line secreting monoclonal rat anti-mouse cell surface antibody (Springer, T., Galfre, G., Secher, D. S. and Milstein, C, Eur. J. Immunol. 1978. 8: 539). We have now investigated the cellular distribution of this antigen using a 125I-labeled anti-rat IgG indirect binding assay, the fluorescence-activated cell sorter, autoradiography and precipitation of cell surface molecules. Screening with a tumor cell panel showed strong reactivity with a macrophage-like line but no reactivity with B or T lymphoma lines. In normal tissues, M1/70 antigen was found to be present in small amounts on spleen and exudate granulocytes and a subpopulation of bone marrow cells, in moderate amounts on spleen and blood monocytes and expressed in much larger amounts on spleen histiocytes and peritoneal exudate macrophages. In contrast, M1/70 antigen was found to be absent from erythroid and lymphoid cells. M1/70 antibody precipitated two polypeptides of 190 000 and 105 000 mol. wt. which were present in much greater amounts on peritoneal exudate macrophages than on spleen cells. The expression on phagocytes of two other antigens identified by monoclonal antibodies M1/69 and M1/9.3 was also examined. Monocytes and granulocytes expressed large amounts of M1/69 and low amounts of M1/70 antigen, while in peritoneal exudate macrophages this pattern was dramatically reversed. M1/70 thus defines a differentiation antigen on mononuclear phagocytes and granulocytes, the expression of which is specifically increased during monocyte maturation. This antibody is the first to be described which recognizes a discrete molecule specific to phagocytes.

Mac‐1: a macrophage differentiation antigen identified by monoclonal antibody

Somatic mutation of immunoglobulin light-chain variable-region genes

Much of the regulation of lymphocyte differentiation is unknown. This, in part, has been due to the inability to develop reliable in vitro assays or long-term cultures of lymphocytes. Consequently, many of the current hypotheses concerning the pathways and regulation of lymphocyte differentiation were obtained from complex in vivo experiments. During recent years, however, new techniques and concepts have evolved which may ultimately allow a critical in vitro dissection of the events in lymphocyte differentiation. The concept that lymphokines, as identifiable and purifiable proteins, mediate reactions that were once attributed to complex cell interactions provides a much more amenable approach for ultimate resolution of the basic biology involved. The observation that certain lymphokines have the capability of supporting the proliferation and growth of specific lymphocytes in vitro as an integral component of their physiological functions provides the unique opportunity to isolate specific intermediates in lymphocyte differentiation. The extent to which these approaches will be capable of unraveling the relationship of various lymphocyte subpopulations is unknown, although the available evidence suggests that the principles thus far established may be central to the regulation of immune responses and consequently may be broadly applicable. In this review, the biology and biochemistry of interleukin-3 (IL-3) are discussed. Many of the properties of lL-3 are similar to lL-2 in that they promote differentiation and are required for growth by various lymphocyte lines. However, unlike lL-2, lL-3 appears to primarily influence a stage or stages of immature lymphocyte differentiation and, therefore, provides the means to dissect in vitro a completely unique aspect of lymphocyte differentiation.

Interleukin 3: Possible Roles in the Regulation of Lymphocyte Differentiation and Growth

Abelson murine leukemia virus (A-MuLV)-transformed fibroblast nonproducer cells were used to prepare A-MuLV stocks containing a number of different helper viruses. The oncogenicity of the A-MuLV stocks was tested by animal inoculation and their ability to transform normal mouse bone marrow cells was measured in vitro. All of the A-MuLV stocks transformed fibroblast cells efficiently. However, only A-MuLV stocks prepared with helper viruses that are highly oncogenic were efficient in vivo and in vitro in hematopoietic cell transformation. In addition, inefficient helpers did not establish a stable infection in lymphoid nonproducer cells. Thus, helper virus has a more central role in lymphoid cell transformation than in fibroblast cell transformation.

/pdf/the-effect-of-helper-virus-on-abelson-virus-induced-31wb51imfn.pdf

The effect of helper virus on Abelson virus-induced transformation of lymphoid cells.

The 50% effective doses of fusarenon X, nivalenol, deoxynivalenol, and 15-acetyldeoxynivalenol required to reduce [3H]thymidine uptake in mitogen-stimulated human lymphocytes by 50% were 18, 72, 140, and 240 ng/ml, respectively. These results indicated that lymphotoxicity of 8-ketotrichothecenes decreased according to the C-4 substituent order acetyl greater than hydroxyl greater than hydrogen, whereas acetylation of position C-15 of deoxynivalenol caused a slight decrease in in vitro toxicity. The 50% effective doses for zearalenone, alpha-zearalenol, beta-zearalenol, alpha-zearalanol, and beta-zearalanol were 3,500, 6,300, 36,000, 3,750, and 33,000 ng/ml, respectively, suggesting that a keto group or alpha-hydroxyl at the position C-6' contributed to the lymphotoxicity of the parent molecule. The inhibitory effects of zearalenone analogs observed in the blastogenesis assay did not correlate with the estrogenic potencies of these compounds. All 8-ketotrichothecenes and zearalenone analogs tested were capable of inhibiting B- and T-cell subsets stimulated by a mitogen panel of leukoagglutinin, concanavalin A, and pokeweed mitogen.

https://aem.asm.org/content/aem/50/5/1304.full.pdf

Relation of 8-ketotrichothecene and zearalenone analog structure to inhibition of mitogen-induced human lymphocyte blastogenesis.

Terminal transferase remains the only good candidate for a somatic-mutation-producing DNA polymerase. It is clearly found that in immature, but not in mature, T cells. It is also found in a population of bone marrow cells that lack an inducible T-cell marker and that could be B-cell precursors (but might well be unrelated to B cells). The most suggestive observation that could be interpreted as evidence for terminal transferase in pre-B cells is the occurrence of activity in Abelson virus-induced tumor cells. The status of Abelson tumor cells is, however, uncertain.

A. E. Silverstone

Papers

Specialized DNA polymerases in lymphoid cells.