Influence of pre-B cell receptor deficiency on the immunoglobulin repertoires in peripheral blood B cells before and after immunization

Abstract

During B cell development, pre-B cell receptor (pre-BCR), comprising the immunoglobulin heavy chain (HC) and surrogate light chain (SLC), plays a crucial role. The expression of pre-BCR serves as a certification of HC quality, confirming its ability to associate with the SLC and light chain (LC). In mice lacking SLC, the absence of this quality control mechanism leads to a distorted repertoire of HCs in the spleen and bone marrow. In this study, we conducted a comparative analysis of the immunoglobulin gene repertoire in peripheral blood cells of both wild-type mice and pre-BCR–deficient mice. Our findings reveal differences not only in the μ HC repertoire but also in the α HC and κ LC repertoires of the pre-BCR–deficient mice. These results suggest that the pre-BCR–mediated quality check of HC influences the selection of class-switched HC and LC repertoires. To further explore the impact of pre-BCR deficiency, we immunized these mice with thymus-dependent antigens and compared the antigen-responding repertoires. Our observations indicate that the affinity maturation pathways remain consistent between wild-type mice and pre-BCR–deficient mice, albeit with variations in the degree of maturation.