Human B cell memory

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Following an immune response two types of differentiated B cells persist in the memory pool: plasma cells, which confer immediate protection by the secretion of specific antibodies; and memory B cells, which confer rapid and enhanced response to secondary challenge. We will review recent advances in understanding the heterogeneity, dynamics, and persistence of human memory B cells and plasma cells as well as new methods to isolate human monoclonal antibodies. These findings offer new insights into the human B cell response, which are relevant for vaccination and therapeutic intervention.

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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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