IDENTIFICATION AND CHARACTERIZATION OF IL-2 HYPER-RESPONSIVE NZB WF1 CD5- B-CELLS/

The responsiveness of CD5(-) and CD5(+) B cells of BALB/c and NZB/WF1 mice to various cytokines was examined with respect to their growth an d differentiation. BALB/c splenic CD5(-) B cells required longer incub ation with IL-2 or pretreatment with IL-4 to respond to IL-2 by DNA sy nthesis, whereas NZB/WF1 CD5(-) B cells were highly competent to IL-2. Flow cytometric analysis demonstrated that NZB/WF1 and BALB/c CD5(-) B cells had higher and intermediate proportions of B cells positive fo r IL-2R beta, respectively. On the other hand, BALB/c and NZB/WF1 sple nic CD5(+) B cells consisted of lower proportion of B cells positive f or IL-2R beta than did their corresponding CD5(-) B cells and grew mea gerly in response to IL-2. Peritoneal exudative CD5(+) B cells of NZB/ WF1 mice lacked IL-2R beta mRNA expression and failed to respond to IL -2. Although both BALB/c and NZB/WF1 CD5(-) B cells pretreated with an ti-IgM, IL-4, and IL-5 responded to IL-2 by DNA synthesis, only BALB/c CD5(-) B cells developed into IgM-producing cells. Furthermore, BALB/ c, but not NZB/WF1 CD5(-), B cells pretreated with anti-IgM and IL-5 r esponded to IL-2 by IgM production without DNA synthesis. Thus, cross- talk between IL-4 and IL-2 operated in the growth responses of both BA LB/c and NZB/WF1 splenic CD5(-) B cells, whereas cross-talk between IL -5 and IL-2 operated only in the differentiation of BALB/c CD5(-) B ce lls, providing us with another intriguing functional abnormality of NZ B/WF1 B cells.