Mice deficient in Complement Receptor 1 produce normal to enhanced quantities of antigen specific immunoglobulin in response to naïve immune challenge (172.14)

Abstract

Complement receptors (Cr)1 and 2 have been established to have important roles in control of complement activation in the immune microenvironment and B cell responses. Previous work investigating the effects of these receptors in vivo has relied on a double knockout mouse line in which each of these receptors was deleted. However, two drawbacks of this mouse must be acknowledged: 1) that both receptors are deleted and roles of each must be inferred, and 2) that the essential B cell signaling protein CD19 is expressed at a significantly higher level than WT cells. We have created a Cr1 deficient line of mice (expressing Cr2) by homologous gene targeting that expresses normal levels of Cr2 gene products on B cells. This animal has normal ratios of bone marrow, B2 cell, and B1 B cell populations. Cr2 negative marrow B cells express the same amount of surface CD19 as WT but mature Cr2-expressing B cells express less. These Cr2-only mice generate normal to slightly enhanced antibody titers to T-dependent and T-independent (both 1 and 2 antigens.) In conclusion Cr1 is not critical for development and maintenance of B cell populations nor for the generation of antibodies to naïve antigens. This mouse, along with the Cr1/2KO, will be a critical tool in delineating Cr1 specific immune response effects.