%0 Journal Article
%T The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression
%A Daniela Fr£¿lich
%A Daniela Bla¦Âfeld
%A Karin Reiter
%A Claudia Giesecke
%A Capucine Daridon
%A Henrik E Mei
%A Gerd R Burmester
%A David M Goldenberg
%A Abdulagabar Salama
%A Thomas D£¿rner
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3767
%X Surface expression of CD74 on CD27- na£¿ve and CD27+ memory B cells as well as other peripheral blood mononuclear cells (PBMCs) obtained from normals, including the co-expression of CD44, CXCR4, and the adhesion molecules CD62L, ¦Â7-integrin, ¦Â1-integrin and CD9 were studied after binding of milatuzumab using multicolor flow cytometry. The influence of the antibody on B-cell proliferation and migration was analyzed in vitro in detail.In addition to monocytes, milatuzumab also specifically bound to human peripheral B cells, with a higher intensity on CD27+ memory versus CD27- na£¿ve B cells. The antibody reduced B-cell proliferation significantly but moderately, induced enhanced spontaneous and CXCL12-dependent migration together with changes in the expression of adhesion molecules, CD44, ¦Â7-integrin and CD62L, mainly of CD27- na£¿ve B cells. This was independent of macrophage migration-inhibitory factor as a ligand of CD74/CD44 complexes.Milatuzumab leads to modestly reduced proliferation, alterations in migration, and adhesion molecule expression preferentially of CD27- na£¿ve B cells. It thus may be a candidate antibody for the autoimmune disease therapy by modifying B cell functions.Milatuzumab is a humanized monoclonal antibody (also called hLL1 or IMMU-115) targeting a cell surface-expressed epitope of the molecule CD74 which is expressed on monocytes, macrophages, and B cells but not T cells [1]. Currently, milatuzumab is a candidate immunotherapeutic antibody being studied in multiple myeloma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL) [1]. B cells of these hematological tumors express the target molecule, CD74, at high levels and internalize it rapidly after milatuzumab binding [2,3]. Consequently, growth inhibition and induction of apoptosis in B-cell lines in the presence of a second cross-linking antibody (for example, Fc¦Ã-specific F(ab)2 fragments to mimic the role of effector cells or cross-linking molecules present in vivo) have been repor
%U http://arthritis-research.com/content/14/2/R54