Abstract
Regional lymph node lymphocytes from five patients with primary lung cancer were analyzed for subset composition, and exposed in vitro to the polyclonal human B cell mitogen Staphylococcus aureus Cowan I (SACI) or the murine B cell mitogen lipopolysaccharide (LPS) and then fused with mouse myeloma cells for investigation at the clonal level of their antibody (Ab) production and its statistical relation to the original subset composition. No correlation was found between the proportion of CD19+, CD23+, or CD3+ cells in the lymphocyte sample prior to its exposure to either SACI or LPS, and the Ab production efficiency, defined as the ratio of the number of Ab producing wells to the total number of proliferating wells. For lymphocytes exposed to LPS, however, a strong correlation (r = 0.931, p = 0.02) was observed between the Ab production efficiency and the ratio of CD8+ to CD3+ cells (CD8/CD3) in the original sample at least within the ranges studied (CD8/CD3 = 0.216–0.288). For those exposed to SACI, no correlation was found between the Ab production efficiency and the CD8/CD3 ratio (r = 0.881, p = 0.12) or the proportion of CD8+ cells (r = 0.808, p = 0.19) in the original sample. These results suggest that the repertoire of B cells responsive to LPS is different at least in part from the repertoire responsive to SACI and that the ratio CD8/CD3 could serve as a practical predictor for Ab production by human lymphocytes stimulated with LPS.
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Cairns E, Germain J St and Bell DA (1985) The in vitro production of anti-DNA antibody by cultured peripheral blood or tonsillar lymphoid cells from normal donors and SLE patients. J Immunol 135: 3839-3844.
Croce CM, Linnenbach A, Hall W, Steplewski Z and Koprowski H (1980) Production of human hybridomas secreting antibodies to measles virus. Nature 288: 488-489.
Farzad Z, Cochran AJ, McBride WH, Gray JD, Wong V and Morton DL (1990) Lymphocyte subset alterations in nodes regional to human melanoma. Cancer Res 50: 3585-3588.
Forsgren A, Svedjelund A and Wigzell H (1976) Lymphocyte stimulation by protein A of Staphylococcus aureus. Eur J Immunol 6: 207-213.
Foung S, Perkins S, Kafadar K, Gessner P, and Zimmermann U (1990) Development of microfusion techniques to generale human hybridomas. J Immunol Methods 134: 35-42.
Haspel MV, McCabe RP, Pomato N, Janesch NJ, Knowlton JV, Peters LC, Hoover Jr HC and Hanna Jr MG (1985) Generation of tumor cell-reactive human monoclonal antibodies using peripheral blood lymphocytes from actively immunized colorectal carcinoma patients. Cancer Res 45: 3951-3961.
Ho M-K, Rand N, Murray J, Kato K and Rabin H (1985) In vitro immunization of human lymphocytes. J Immunol 135: 3831-3838.
Imam A, Drushella MM, Taylor CR and Tökés ZA (1985) Generation and immunohistological characterization of human monoclonal antibodies to mammary carcinoma cells. Cancer Res 45: 263-271.
Jahn S, Grunow R, Kiessig ST, Specht U, Matthes H, Hiepe F, Hlinak A and von Baehr R (1988) Establishment of human Ig producing heterohybridomas by fusion of mouse myeloma cells with human lymphocytes derived from peripheral blood, bone marrow, spleen, lymph node, and synovial fluid. J Immunol Methods 107: 59-66.
Kan-Mitchell J, Imam A, Kempf RA, Taylor CR and Mitchell MS (1986) Human monoclonal antibodies directed against melanoma tumor-associated antigens. Cancer Res 46: 2490-2496.
Kipps TJ and Duffy SF (1991) Relationship of the CD5 B cell to human tonsillar lymphocytes that express autoantibody-associated cross-reactive idiotypes. J Clin Invest 87: 2087-2096.
Kjeldsen T, Rasmussen BB, Rose C and Zeuthen J (1988) Humanhuman hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocytes from breast cancer patients. Cancer Res 48: 3208-3214.
Nakashima M, Watanabe T, Koprowski H and Steplewski Z (1996) HLA-B-restricted, CD8+ cytolytic human T cell clones derived from a melanoma-invaded lymph node. Hybridoma 15: 147-154.
Nozawa S, Narisawa S, Kojima K, Sakayori M, Iizuka R, Mochizuki H, Yamauchi T, Iwamori M and Nagai Y (1989) Human monoclonal antibody (HMST-1) against lacto-series type 1 chain and expression of the chain in uterine endometrial cancers. Cancer Res. 49: 6401-6406.
Ringdén O and Rynnel-Dagöö B (1978) Activation of human B and T lymphocytes by protein A of Staphylococcus aureus. Eur J Immunol 8: 47-52.
Ruuskanen O, Pittard III WB, Miller K, Pierce G, Sorensen RU and Polmar SH (1980) Staphylococcus aureus Cowan I-induced immunoglobulin production in human cord blood lymphocytes. J Immunol 125: 411-413.
Schuurman RKB, Gelfand EW and Dosch H-M (1980) Polyclonal activation of human lymphocytes in vitro. J Immunol 125: 820-826.
Siroka K (1987) Human monoclonal antibodies to cancer cells. In: Strelkauskas AJ (ed.) Human hybridomas. Marcel Dekker Inc., New York, pp. 159-181.
Tsujitani S, Nakashima M, Watanabe T, Kaibara N, Koprowski H and Steplewski Z (1995) Cytokine combinations for induction of antigen-specific cytolytic T lymphocytes from peripheral blood lymphocytes. Anticancer Res 15: 655-660.
Umetsu DT and Geha RS (1987) In vitro production of antibody in culture of human peripheral blood lymphocytes. Methods in Enzymol 150: 309-316.
Warenius HM, Taylor JW, Durack BE and Cross PA (1983) The production of human hybridomas from patients with malignant melanoma. The effect of pre-stimulation of lymphocytes with pokeweed mitogen. Eur J Cancer Clin Oncol 19: 347-355.
Wright SD, Ramos RA, Tobias PS, Ulevitch RJ and Mathison JC (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249: 1431-1433.
Yoshinari K, Arai K, Kimura H, Matsumoto K and Yamaguchi Y (1995) Long-term production of human monoclonal antibodies by heterohybridomas. J Immunol Methods 186: 17-25.
Yoshinari K, Arai K, Kimura H, Matsumoto K and Yamaguchi Y (1996) Efficient production of IgG human monoclonal antibodies by lymphocytes stimulated by lipopolysaccharide, pokeweed mitogen, and interleukin 4. In Vitro Cell Dev Biol Animal 32: 372-377.
Ziegler-Heitbrock HWL and Ulevitch RJ (1993) CD14: cell surface receptor and differentiation marker. Immunol Today 121: 121-125.
Zimmermann U, Gessner P, Schnettler R, Perkins S and Foung SKH (1990) Efficient hybridization of mouse-human cell lines by means of hypo-osmolar electrofusion. J Imunol Methods 134: 43-50.
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Yoshinari, K., Arai, K., Matsumoto, K. et al. Relationship between antibody productivity by activated human lymph node lymphocytes from lung cancer patients and lymphocyte subsets. Cytotechnology 29, 229–236 (1999). https://doi.org/10.1023/A:1008052326963
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DOI: https://doi.org/10.1023/A:1008052326963