Soluble Fc Receptor for IgM in Sera From Subsets of Patients With Chronic Lymphocytic Leukemia as Determined by a New Mouse Monoclonal Antibody

The FcR for IgM (FcµR) is the newest member of the FcR family, selectively expressed by lymphocytes, and distinct from FcRs for switched Ig isotypes that are expressed by various immune cell types and non-hematopoietic cells. From studies of Fcmr -ablated mice, FcµR was shown to have a regulatory fu...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in immunology Vol. 13; p. 863895
Main Authors Mahmoudi Aliabadi, Pedram, Teuber, Ruth, Jani, Peter K., Wilson, Landon, Enghard, Philipp, Barnes, Stephen, Chiorazzi, Nicholas, Radbruch, Andreas, Melchers, Fritz, Kubagawa, Hiromi
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 16.06.2022
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:The FcR for IgM (FcµR) is the newest member of the FcR family, selectively expressed by lymphocytes, and distinct from FcRs for switched Ig isotypes that are expressed by various immune cell types and non-hematopoietic cells. From studies of Fcmr -ablated mice, FcµR was shown to have a regulatory function in B-cell tolerance, as evidenced by high serum titers of autoantibodies of the IgM and IgG isotypes in mutant mice. In our previous studies, both cell-surface and serum FcµR levels were elevated in patients with chronic lymphocytic leukemia (CLL), where antigen-independent self-ligation of BCR is a hallmark of the neoplastic B cells. This was assessed by sandwich ELISA using two different ectodomain-specific mAbs. To determine whether the serum FcµR is derived from cleavage of its cell-surface receptor (shedding) or its alternative splicing to skip the transmembrane exon resulting in a 70-aa unique hydrophilic C-terminus (soluble), we developed a new mouse IgG1κ mAb specific for human soluble FcμR (solFcμR) by taking advantages of the unique nature of transductant stably producing His-tagged solFcµR and of an in vivo differential immunization. His-tagged solFcμR attached to exosomes and plasma membranes, allowing immunization and initial hybridoma screening without purification of solFcμR. Differential immunization with tolerogen (membrane FcμR) and immunogen (solFcμR) also facilitated to generate solFcμR-specific hybridomas. The resultant solFcμR-specific mAb reacted with serum FcµR in subsets of CLL patients. This mAb, along with another ectodomain-specific mAb, will be used for verifying the hypothesis that the production of solFcµR is the consequence of chronic stimulation of BCR.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by: Deborah K Dunn-Walters, University of Surrey, United Kingdom
Reviewed by: Paolo Ghia, Vita-Salute San Raffaele University, Italy; Gregory C Ippolito, University of Texas at Austin, United States
This article was submitted to B Cell Biology, a section of the journal Frontiers in Immunology
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.863895