Regeneration of the immunoglobulin heavy-chain repertoire after transient B-cell depletion with an anti-CD20 antibody

Our data show that therapeutic transient B-cell depletion by anti-CD20 antibodies results in the regeneration of a diverse and polyclonal heavy-chain repertoire. During the early phase of B-cell regeneration, highly mutated B cells recirculate for a short time period in both the patients analysed. The longitudinal observation of a single patient up to 27 months shows subtle intraindividual changes, which may indicate repertoire modulation.Although the role of B cells in autoimmunity is not completely understood, their importance in the pathogenesis of autoimmune diseases has been further appreciated in the past few years. It is now well known that B cells are more than just the precursors of (auto)antibody-secreting cells [1-4]. They are also involved in the regulation of T-cell-mediated autoimmune diseases by different mechanisms. In this regard, B cells are very efficient antigen-presenting cells. Activated B cells express co-stimulatory molecules, such as CD154, and in this way contribute to the evolution of T effector cells. They can produce chemokines and cytokines, like lymphotoxin α/β, that are essential for the differentiation of follicular dendritic cells in secondary lymphoid organs and for the organisation of effective lymphoid architecture.There are also indications that B-cell activity is enhanced in rheumatoid arthritis (RA) [2,5]. B cells are found in the synovium, where they form aggregates with T cells and develop tertiary lymphoid tissue structures [5]. The mutational activity of these B cells is markedly enhanced and abnormalities in positive selection and negative selection are found [2]. Furthermore, elimination of B cells by anti-CD20 antibodies from the synovial tissue provokes a disruption of T-cell activation and provokes the production of proinflammatory monokines [6], proving an important role of B cells in the pathogenesis of RA.The B-cell repertoire is shaped by a complex set of gene rearrangements, somatic hypermutation and receptor-dri