Responses to rituximab vary among follicular lymphoma B cells of different maturation stages

A. M Mattila, Seppo Meri

Research output: Contribution to journalArticleScientificpeer-review

Abstract

The chimeric anti-CD20 monoclonal antibody rituximab has been used for the treatment of non-Hodgkin's lymphomas with varying responses. Rituximab has been demonstrated to act by direct complement-dependent cytotoxity (CDC) and by inducing apoptosis, complement-, and antibody-dependent cellular cytotoxity. In the present study, we determined whether rituximab's effector mechanisms differed between two human follicular lymphoma cell lines that originate from different maturation stages of B cell germinal centre (GC) development. The tested HF-1 and HF-4b lymphoma cells represent GC centrocytes and centroblasts, respectively. Both cell lines responded to rituximab treatment by undergoing apoptosis yet the HF-1 cells were more sensitive. A major difference was seen in the proliferation response as only the proliferation of HF-1 cells was inhibited by rituximab. In the presence of normal human serum (NHS) rituximab almost completely inhibited DNA synthesis and induced necrosis of both cell lines because of CDC. Our results show that the CD20-positive HF-1 and HF-4b cells respond differentially to rituximab-induced apoptosis and inhibition of proliferation but similarly to complement-mediated killing. The increased sensitivity of the HF-1 cell line to apoptosis and inhibition of proliferation may reflect a tendency of centrocytic cells for negative selection and a role for CD20 in this process.
Original languageEnglish
JournalScandinavian Journal of Immunology
Volume68
Issue number2
Pages (from-to)159-168
Number of pages10
ISSN0300-9475
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

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