Introduction: T-dependent (DT) and T-independent (TI) antigens induce the polyclonal activation of B cells and nonspecific Ig formation. Mechanism of polyclonal activation under the influence of TI-antigens of type 2 (TI-2) is unclear. In mice anti-TI-2 antibodies are produced by Lyb5+ B cells. The present study was done to determine which of B cell subpopulations is responsible for the nonspecific Ig formation induced by TI-2.Materials and Methods: Congenic mice CBA and CBA/N and C57BI/6 and bm12 were used. Influenza virus and watersoluble antigen of sheep red blood cells were used as TD-antigens and DNP-Ficoll and polyvinylpirrolidon as TI-2 antigens. Specific and polyclonal immune responses were studied in vivo and in vitro. Antibody- and Ig-forming cells (AFC and IFC, respectively) were determined by ELISPOT.Results: Immunization of C57BI/6 and bm12 mice by TD- and TI-2 antigens induced an increase in AFC and IFC number in both strains, more pronounced with TD-antigens. Immunization by the same TD-antigens of CBA and CBA/N mice induced a strong increase in the number of AFC and IFC in both strains also. On the contrary, immunization by TI-2 antigens resulted in the marked augmentation of AFC and IFC numbers only in CBA, but not in CBA/N mice. Similar data were obtained in in vitro experiments. It is known that bm12 mice lack one of the markers of the mature B cells (Ia.W39) while CBA/N mice lack the whole of Lyb5+ B cell subpopulation. The data received point out that the absence of Lyb5+ B cells exerts profound effect not only on specific but also on polyclonal immune response to TI-2.Conclusion: Polyclonal B cell activation induced by TI-2 antigens in mice depends on Lyb5+ B cell subpopulation.