Heat-shock proteins: a c-Myc lymphoma target?

the BM, because fewer somatic mutations were detected in immunoglobulin variable genes of CD19 2 PCs than in CD19 1 PCs, implying that these PC subsets arise at different times from different precursors during the evolution of the GC response. Remarkably, despite comparable expression of CD20 by CD19 1 and CD19 2 BMPCs, only CD19 1 BMPCs were reduced by therapeutic B-cell depletion with rituximab, thereby suggesting that CD19 2 BMPCs are less dependent on circulating mature B cells for their generation/replenishment than CD19 1 BMPCs. Similarly, although both antigen-specific and-nonspecific PCs were detected in peripheral blood 1 week after tetanus vaccination, 1,9 none of these cells shared the phenotypic or molecular characteristics of CD19 2 BMPCs, implying that they are more " embedded " in their survival niche than are CD19 1 BMPCs and that they are the " fitter " subset of long(er)-lived PCs. Importantly, CD19 2 PCs were also detected in inflamed tissues and BM of autoimmune patients and could produce autoreactive IgG. 1 Thus, although rituximab can deplete short-lived plasmablasts and improve disease in some settings of autoimmunity, 10 targeting these long-lived PCs will also be necessary for effective or improved therapeutic approaches to treating these disorders. This study has reminded us of, and further defined, the heterogeneity and complexity that exist within what we generally consider to be the pool of human long-lived PCs. 1,7 It also provides a possible explanation for the varying serum half-lives of protective Abs, with some antigens/ pathogens perhaps preferentially inducing CD19 2 vs CD19 1 PCs. Now, understanding how this could be achieved for all antigens may allow us to avoid future plagues that Thucydides so famously and accurately documented. Conflict-of-interest disclosure: The author declares no competing financial interests. n REFERENCES 1. Mei HE, Wirries I, Frölich D, et al. A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow.secreting cells persist in human spleen and bone marrow. The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression. Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Heat-shock proteins: a c-Myc lymphoma target? In this issue of Blood, Zappasodi et al show that heat-shock protein 105 (HSP105/ HSPH1) is preferentially expressed in aggressive B-cell lymphomas, it modulates BCL-6 and c-Myc …