Clinical Significance of CD21 Co-Expressed with LFA-1 in Non-Hodgkin’s B-Cell Lymphoma.
Authors: Tanimoto Kazushi , Yakushijin Yoshihiro , Fujiwara Hiroshi , Otsuka Masaki , Ohshima Koichi , Sugita Atsuro , Sakai Akira , Hato Takaaki , Hasegawa Hitoshi , Yasukawa Masaki 
Published: April 2020

Abstract
Since non-Hodgkin’s lymphoma is a disease of heterogeneous lymphoid malignancies, precise classification is essential for predicting the prognosis and determining the appropriate treatment strategy. Although the recent studies of gene expression profiling-based classification have successfully discriminated diffuse large B-cell lymphoma (DLBCL) into two subgroups based on the origin of lymphoma cells and their prognosis, this method is hardly applicable for the routine practice due to complexity of techniques. Because the immunohistochemistry-based classification of non-Hodgkin’s lymphoma can be easily applicable, it has been widely used in daily practice. We previously reported the favorable prognostic value of CD21 for DLBCL (Br J Haematol.2004;127:416–424). Although the research for function of CD21 in normal B lymphocytes has been progressed, little is known about the biological significance of CD21 in progression of B-cell lymphoma (BCL) line cells. Based on these backgrounds, we attempted to clarify the biological characteristics of CD21 in BCL and to determine the clinical significance of CD21 expression focusing on the mechanisms of progression and dissemination of BCL cells. To examine the characteristic changes in lymphoma cells induced by CD21 expression, CD21 gene was transfected in CD21-negative lymphoma cell line, Namalwa. The characteristics of CD21 gene-transfected B-cell lymphoma cell lines (CD21-transfectants) were compared to those of a parent CD21-negative cell line. Established clones of CD21-transfectants showed homotypic aggregation in suspension culture. Analysis of integrin expression revealed that LFA-1 (CD11a/CD18) appeared to be newly expressed on CD21-transfectants at a transcriptional level. The CD21-tranfectants could bind on plastic plate coated with ICAM-1, and ICAM-1 expression was detected on both CD21-transfectants and a parent BCL line. Cell aggregation was abrogated by adding an anti-LFA-1 antibody. Based on the findings obtained from experiments, biopsy samples of BCL (n=29) and BCL cells isolated from pleural or peritoneal cavity fluid (n=10) were analyzed by flow cytometry and/or immunohistochemical staining. Consequently, all cases positive for CD21 appeared to co-express LFA-1 unexceptionally, as observed in CD21-transfectants. Interestingly, all BCL cells isolated from pleural or peritoneal cavity fluid appeared to express neither CD21 nor LFA-1. Our data strongly suggest that absence of CD21 expression in BCL seems to correlate with lymphoma dissemination, which might be partially resulted from lacked interaction between CD21-related LFA-1 and ICAM-1, as shown in the figure. In summary, the present study demonstrates for the first time the biological significance of co-expression of CD21 and LFA-1 in the pathogenesis of lymphoma progression. Our data may shed light on understanding the mechanisms responsible for dissemination of lymphoma cells and further studies focusing on the association of CD21 and adhesion molecules are expected to develop the novel strategy for lymphoma treatment.
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