Abstract
In humans, different B-cell subpopulations can be distinguished in peripheral blood and other tissues on the basis of differential expression of various surface markers. These different subsets correspond to different stages of maturation, activation and differentiation. B-cell depletion therapy based on rituximab, an anti-CD20 mAb, is widely used in the treatment of various malignant and autoimmune diseases. Rituximab induces a very significant depletion of B-cell subpopulations in the peripheral blood usually for a period of 6 to 9 months after one cycle of therapy. Cells detected circulating during depletion are mainly CD20 negative plasmablasts. Data on depletion of CD20-expressing B cells in solid tissues are limited but show that depletion is significant but not complete, with bone marrow and spleen being more easily depleted than lymph nodes. Factors influencing depletion are thought to include not only the total drug dose administered and distribution into various tissues, but also B-cell intrinsic and microenvironment factors influencing recruitment of effector mechanisms and antigen and effector modulation. Available studies show that the degree of depletion varies between individuals, even if treated with the same dose, but that it tends to be consistent in the same individual. This suggests that individual factors are important in determining the final extent of depletion.
Highlights
Introduction toB-cell subpopulations In humans from birth all new B cells originate from common precursors in the bone marrow
Marginal zone B cells can be found in the marginal zone of the spleen and similar populations are described in particular locations in other secondary lymphoid tissues [1]
B cells stimulated in the presence of rituximab induced stronger T-cell proliferation and the T-cell population showed a more Th2-like phenotype. These results suggest that B cells which are exposed to rituximab but are not depleted may have altered function and that naïve and memory B cell populations may be differentially affected
Summary
Introduction toB-cell subpopulations In humans from birth all new B cells originate from common precursors in the bone marrow. Studies in autoimmune diseases – in particular, RA and systemic lupus erythematosus – have documented variable degrees and durations of B-cell depletion in peripheral blood in different individuals following treatment with rituximab with standard doses [17,36,37, 39,40,41].
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