Immunoglobulin Deficient Mice Generated by Gene Targeting as Models for Studying the Immune Response

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Abstract
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 of μMT, 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 in μMT 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 with P. chabaudi adami, P. vinckei petteri and P. chabaudi chabaudi (CB), B cell compartment is important in the later stages of infection with P. chabaudi chabaudi (AS). Studies carried out in μMT model suggested a possible role for Tγδ subpopulation 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 in μMT 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.