Activated human B cells: stimulatory or tolerogenic antigen-presenting cells?

摘要

In recent years the antibody-independent functions of B cells have gained increasing attention. B cells can become potent antigen-presenting cells (APCs) after activation. Contrary to activated B cells, resting B cells can act as immunoregulatory cells. Two interesting recent papers in Blood now show that activated human B lymphocytes can also obtain regulatory functions. The fact that activated B cells can inhibit T-cell responses is somewhat surprising, as we and others have shown that B cells stimulated via CD40 induce CD4~+ and CD8~+ T-cell responses in vitro and in vivo.1'3 How can these discrepancies be explained? Tretter et al show that activation by Staphylococcus aureus Cowan I (SAC) or CpG-containing oligonucleotides induces B cells which down-regulate T-cell responses by inducing anergy and apoptosis of CD4~+ T cells in an IL-2-dependent fashion. The suppressive effect was restricted to the activated large B-cell subpopulation expressing the high-affinity interleukin-2 (IL-2) receptor CD25. CD25 expression is not a marker for B cells with regulatory function, though, because many other stimuli, including CD40 activation and IL-4, also induce CD25 expression. Like the regulatory B-cell population described by Tretter et al, CD40-activated B cells express CD25 as well as high levels of costimula-tory molecules (Figure 1). Despite these similar features, they do activate T cells even in the presence of 50 U/mL IL-2, a concentration at which Tretter et al observed an inhibition of T-cell proliferation. Therefore, the functional consequences of CD25 expression on activated B cells appear to be dependent on the activation stimulus. Bacterial activation by stimuli such as CpG, SAC, and lipopolysaccharide seem to confer regulatory functions whereas activation via CD40 induces stimulatory functions in B cells exposed to IL-2. In addition, because SAC preferentially activates; immunoglobulin variable heavy chain gene 3 (VH3)-expressing B cells, it could be that suppressive function is characteristic for this subpopulation of B cells.