Insights into B cell ontogeny inferred from human immunology.

Due to ontogenetic changes in B cell developmental lineages, the mature B cell compartment constitutes by functionally different B cell subsets that emerged from prenatal, early postnatal or adult precursors. While negative selection processes operate primarily within the framework of B cell tolerance checkpoints during B cell development, further differentiation into distinct B cell subsets is additionally induced by positive selection. In addition to endogenous antigens, contact with microbial antigens is also involved in this selection process, with intestinal commensals having a significant influence on the development of a large layer within the B cell compartment. The decisive threshold that triggers negative selection seems to be relaxed during fetal B cell development, thereby allowing recruitment of polyreactive and also autoreactive B cell clones into the mature naïve B cell compartment. Almost all of the concepts on B cell ontogeny are based on observations in laboratory mice that not only differ from humans in their developmental timeline but also in their composition of commensal microorganisms or rather a lack of exposure to these. In this review, we summarize conceptual findings on B cell ontogeny and particularly describe key insights into the developing human B cell compartment and immunoglobulin repertoire formation. This article is protected by copyright. All rights reserved.