Because of the ever-increasing number of pathogenic organisms and their rapid mutation rates, the humoral immune system must have the ability to adapt and change along with evolving pathogens. The ability to rearrange germline antibody receptors during B-cell development and then modify these receptors in germinal centers is a means of ensuring that the antibody repertoire diversifies to be able to expunge a broad range of pathogens. However, the randomness of the mechanisms involved in diversifying the antibody repertoire can also generate specificities that attack the host. Because of this, strict regulation of B-cell development and activation is utilized to maintain humoral self tolerance. In this chapter, we broadly overview B-cell biology and the mechanisms used to introduce diversity into the antibody repertoire. We also discuss checkpoints that occur during development that ensure maintenance of self-tolerance. Finally, we discuss the special role that the inhibitory Fc receptor, FcγRIIB, plays in maintaining humoral tolerance.
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