BCR activated CLL B cells use both CR3 (CD11b/CD18) and CR4 (CD11c/CD18) for adhesion while CR4 has a dominant role in migration towards SDF-1

Zsuzsa Nagy-Baló; Richárd Kiss; Judit Demeter; Csaba Bödör; Zsuzsa Bajtay; Anna Erdei

doi:10.1371/journal.pone.0254853

BCR activated CLL B cells use both CR3 (CD11b/CD18) and CR4 (CD11c/CD18) for adhesion while CR4 has a dominant role in migration towards SDF-1

PLoS One. 2021 Jul 20;16(7):e0254853. doi: 10.1371/journal.pone.0254853. eCollection 2021.

Authors

Zsuzsa Nagy-Baló^{1

2}, Richárd Kiss³, Judit Demeter⁴, Csaba Bödör³, Zsuzsa Bajtay^{1

2}, Anna Erdei^{1

2}

Affiliations

¹ Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
² MTA-ELTE Immunology Research Group, Eötvös Loránd University, Budapest, Hungary.
³ MTA-SE Momentum Molecular Oncohematology Research Group, First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
⁴ Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary.

Abstract

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world. In previous studies, various proportion of patients was found to carry CD11b+ or CD11c+ B cells whose presence was an unfavourable prognostic factor. The exact mechanism however, how these receptors contribute to the pathogenesis of CLL has not been revealed so far. Here we analysed the role of CD11b and CD11c on B cells of CLL patients in the adhesion to fibrinogen and in the migration towards stromal cell derived factor-1 (SDF-1) and studied the role of CR4 in the adherence of the CD11c+ B cell line BJAB. We observed that both CR3 and CR4 mediate adhesion of the malignant B cells. Moreover, we found, that CR4 was strongly involved in the migration of the leukemic cells towards the chemoattractant SDF-1. Our data suggest that CR3 and CR4 are not only passive markers on CLL B cells, but they might contribute to the progression of the disease. Since the role of SDF-1 is prominent in the migration of CLL cells into the bone marrow where their survival is supported, our findings help to understand how the presence of CD11c on leukemic B cells can worsen the prognosis of chronic lymphocytic leukaemia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
B-Lymphocytes / immunology
B-Lymphocytes / metabolism*
CD11b Antigen / immunology
CD11b Antigen / metabolism*
CD11c Antigen / immunology
CD11c Antigen / metabolism*
CD18 Antigens / metabolism
Cell Adhesion / immunology
Cell Movement / physiology
Chemokine CXCL12 / metabolism
Female
Fibrinogen / metabolism
Humans
Integrin alphaXbeta2
Leukemia, Lymphocytic, Chronic, B-Cell / immunology
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
Macrophage-1 Antigen / metabolism
Macrophages / metabolism
Male
Middle Aged
Phagocytosis

Substances

CD11b Antigen
CD11c Antigen
CD18 Antigens
CXCL12 protein, human
Chemokine CXCL12
ITGAM protein, human
Integrin alphaXbeta2
Macrophage-1 Antigen
Fibrinogen

Grants and funding

This work was supported by the National Research Fund (National Research, Development and Innovation Office), grant No.: K112011 and by the Hungarian Academy of Sciences (MTA). Research was completed as part of the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office (TKP2020-IKA-05) and as part of the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary within the framework of the Molecular Biology thematic programme of the Semmelweis University and the ELIXIR Hungary. Flow cytometry measurements were performed using a CytoFLEX cytometer provided by the grant Széchenyi 2020, No.: VEKOP-2.3.3-15-2017-00021. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.