B cell deficient animals obtained by various strategies of gene targeting were used to study the B cell development and examine the role of different immune compartments in the immune response to microbes.Study ofμMT, JHD,AST and JHT models of B cell deficiency, was essential in order to understand the role of pre-B cell receptor in B cell development, allelic exclusion and variable gene rearrangement regulation.In the immune response to influenza virus, a protective role of T cells in a total absence of B cell compartment, was revealed by studying the JHD -/- model. Further, it was established that a T cell compartment is sufficient to mediate the recovery from influenza infection.Examination of immune response inμMT and JHD models of definitive B cell deficiency to various blood stage Plasmodia species, showed that whereas B cells are not required for recovery from infection withP. chabaudi adami, P. vinckei petteriandP. chabaudi chabaudi(CB), B cell compartment is important in the later stages of infection withP. chabaudi chabaudi(AS). Studies carried out inμMT model suggested a possible role for Tγδsubpopulation in the immune response to blood stage malaria parasite.B cell deficiency models are valuable for understanding the normal and pathological immune response. Studies carried out inμMT model indicated that T cell responses are not significantly affected in the absence of B cells. These data can neither rule out a role for B cells in T cell priming, nor in triggering an effective T cell help for humoral response. Study of double homozygous mice deficient for B cells and FAS or IL-2 gene, pinpointed the role of B cells in pathogenesis of lupus-like nephritis and vasculitis from lpr mouse and in hemolytic anemia from IL-2 -/- mouse model, respectively.