A new reliable and highly specific monoclonal antibody to detect the C-terminal region of silencer of cytokine signaling 1

Eur J Haematol. 2021 Jul;107(1):74-80. doi: 10.1111/ejh.13620. Epub 2021 May 6.

Abstract

Introduction: SOCS1, a negative regulator of JAK/STAT signaling, is among the most frequently mutated genes in DLBCL and classical Hodgkin lymphoma. The C-terminal SOCS box domain, mediating the degradation of phospho-JAK2, is often affected or even lacking. The analysis of such variants is hampered by the lack of a SOCS1-specific monoclonal antibody recognizing the C-terminus of SOCS1. As this C-terminus is often lost or mutated in B-cell lymphomas, staining with amino-terminal targeting antibodies in a lymphoma setting might be misleading.

Methods: BALB/c mice were immunized with a truncated SOCS1 C-terminal protein. The supernatant of generated hybridoma cells was screened by ELISA and, immunohistochemically, on formalin-fixed and paraffin-embedded tonsil. After antibody purification by affinity chromatography, epitope mapping and cross-reactivity check followed via substitution scans. SOCS1 protein expression was investigated on cell cultures and cytoblocks of SOCS1WT stably transfected HEK293T cells, lymphoma cell lines and lymphoid tissues.

Results: Procedures resulted in one monoclonal IgG1 anti-SOCS1 antibody, 424C, that recognizes and strongly binds to the C-terminal region of SOCS1 in immunoblot and immunohistochemistry analyses.

Conclusion: This new anti-SOCS1 monoclonal antibody is a valuable tool to detect SOCS1 expression dependent on an existing SOCS1 box and, therefore, indicating a full-length SOCS1 protein.

Keywords: B-cell lymphoma; SOCS1; immunohistochemistry; monoclonal antibody; mutation.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Binding Sites
  • Epitope Mapping
  • Epitopes / chemistry
  • HEK293 Cells
  • Humans
  • Hybridomas / metabolism
  • Lymphoid Tissue / metabolism
  • Lymphoma / metabolism
  • Lymphoma, B-Cell / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Palatine Tonsil / metabolism
  • Protein Domains
  • Signal Transduction
  • Suppressor of Cytokine Signaling 1 Protein / chemistry*
  • Suppressor of Cytokine Signaling 1 Protein / metabolism
  • Transfection

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein