Human B cell memory
Section snippets
Longevity of B cell memory
It is well established that in the course of a T cell-dependent B cell response naïve B cells proliferate and differentiate to memory B cells and long-lived plasma cells [1, 2•, 3]. Using highly purified human naïve B cells it was shown that optimal expansion, differentiation, and class switch requires, in addition to BCR triggering and T cell help, a third signal that can be delivered by TLR agonists or by cytokines produced by activated dendritic cells [4]. These findings are consistent with
Human B cell and plasma cell subsets
Subsets of memory B cells and plasma cells can be defined on the basis of the expression of surface markers. Although CD27 has been widely used as a marker for memory B cells [26], there is a substantial fraction of bona fide memory B cells that lack CD27 expression [20]. These CD27-memory B cells have been mistakenly taken as naïve cells, a fact that has generated some confusion in the field. The ABCB1 transporter is expressed exclusively on human mature naive B cells but not on immature,
Human marginal zone B cells
In humans a large fraction of circulating B cells are IgMhi IgDlo CD27+ and carry somatically mutated Ig genes [26]. These cells have been initially considered to be IgM memory B cells, but subsequent studies indicate that they represent a distinct population related to mouse marginal zone (MZ) B cells [34••]. Although they share many properties with their mouse counterpart, such as the response to bacterial polysaccharides, human MZ B cells display striking differences, such as the presence of
Dynamics of memory B cells and plasma cells
Upon booster immunization, memory B cells expand rapidly and generate a burst of plasma cells that peak on day 7 in peripheral blood. At this time point the number of circulating plasma cells can exceed by 100-fold the baseline level and this increase is accounted for primarily by antigen-specific plasma cells [22, 46•]. The plasma cell burst coincides with a sharp increase in serum antibodies that reaches plateau levels on day 10, indicating that the vast majority of the plasma cells generated
Autoreactivity and multispecificity
Autoreactive B cells which are formed as a consequence of random Ig gene recombination are removed at two checkpoints before maturation into naïve B cells and are virtually absent in MZ B cells [50]. Surprisingly however self-reactive antibodies, including antinuclear antibodies, were frequently expressed by IgG+ memory B cells in healthy donors [51••]. Most of these antibodies were created de novo by somatic hypermutation during the transition between mature naive and IgG+ memory B cells. This
B cells and plasma cells as therapeutic targets
In the last few years B cell and plasma cell depletion has provided new opportunities for treatments of malignancies and autoimmune diseases. The anti-CD20 antibody Rituximab, which targets B cells but not plasma cells, has been approved for the treatment of B cell lymphomas and rheumatoid arthritis and has been used to treat chronic lymphocytic leukemia and autoimmune diseases mediated by autoreactive antibodies, such as systemic lupus erythematosus (SLE) and pemphigus. Therapeutic effects
Monoclonal antibodies from memory B cells and plasma cells
In the last five years several methods have been reported to retrieve monoclonal antibodies from human memory B cells and plasma cells. Much of the impetus for these studies derives from the need to develop antibodies that effectively neutralize human pathogens. Broadly neutralizing antibodies could be used not only as therapeutics, but also as tools to design vaccines capable of eliciting a broadly neutralizing response [66•]. An improved method of EBV immortalization has been used to isolate
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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2017, Human ImmunologyCitation Excerpt :Some bias in the correct assignment of DSA at transplant might have occurred, given the known limitations of SAB assay [20]. Moreover, early post-KT ABMR, although typically associated with preformed DSA, may result from cryptic allosensitization in which some anti-HLA antibodies undetectable before transplant reemerge soon after [21,22]. Nevertheless, ABMR in NDSA patients occurred much later (median, 105 days post-KT) than in DSA patients (median, 12 days post-KT), supporting the notion that NDSA association with ABMR resulted from the emergence of de novo DSA and not from post-KT anamnestic humoral response.
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