Evidence for involvement of B lymphocytes in the surveillance of lung metastasis in the rat

These studies examined the composition of lymphocytes within the lung after the introduction of tumor cells that metastasize to the lung in rats. i.v. delivery of MADB106 tumor cells into syngeneic Fischer 344 rats caused dos e- and time-dependent development of lung tumors, with surface metastases e vident 7 days after injection and markedly increased 11 das after injection . The total number of lymphocytes recovered from the lung was increased 11 days after injection hut not 7 days after injection, When lymphocytes from the lung, spleen, and blood were subjected to fluorescence-activated cell s orting analysis, the most conspicuous change nas an increase in the percent age of CD45RA + cells (i.e., B lymphocytes in the rat) in the lung, with no changes seen in the percentage of natural killer (NKR-P1+), CD4+, or CD8cells in the lung. Analysis of the time course showed that B lymphocytes in creased in the lung soon after i.v. tumor injection, with an initial peak s een 6 h after injection. Rapid influx of B lymphocytes into lung after i.v, tumor cell injection Has also observed in another syngeneic tumor model, i .e., after injection of CC531 cells into WAG rats. To determine whether the influx of B lymphocytes into the lung might participate in tumor surveilla nce, a high dose of antibody (100 mu g to rat B lymphocytes was given to im munoneutralize these cells; this produced an increase in lung tumors in bot h models. Finally, Fischer 344 rats Here given a s.c, injection of MADB106 tumor cells that made them resistant to lung tumors when given a later i.v. injection of these tumor cells. These animals were found to have an elevat ed level of B lymphocytes residing in the lung associated with the resistan ce to lung tumor. These findings suggest that early responses of B lymphocy tes are important in protection against tumor development in two rat models of cancer.