Akademiliv

Sahlgrenska akademins nyheter

På Svenska
University of Gothenburg Logotype
  • News
  • Notices
  • Grants
  • About Akademiliv

New insight into receptors on the surface of B cells – relevant for cancer treatment

14 October, 2022

NEW STUDY. A study by researchers in the Department of Rheumatology and Inflammation identifies a mechanism in the signal system that activates B cells. The findings could enable new ways of treating cancer diseases caused by B cells becoming malignant, such as certain forms of lymphoma.

This research is fundamental and increases the understanding of the cascade of signals that lead to activation of a B cell when it encounters viruses, bacteria, or other pathogens in the body. This first leads to the cell dividing (proliferating) and then starting to secrete just the antibody needed to deal with that particular invader. The study concerns mechanisms that are activated when the membrane-bound antibody on the surface of the B cell (the B cell receptor IgM-BCR) binds its specific pathogen. This leads to the cell dividing and then differentiating into a plasma cell, which is a type of cell that secretes large amounts of antibodies, initially IgM.

The findings are highly relevant for cancer research, as the critical molecule (the protein CD38) is highly overexpressed in almost all forms of cancer involving B cells.

The findings have been published by the Journal of Experimental Medicine.

Chance led to a new direction

It was a pure chance that Alessandro Camponeschi started investigating CD38. As a newly minted postdoctoral fellow in Lill Mårtensson-Bopp’s team, he worked on labeling cells with antibodies and sorting them into different cell populations.

Alessandro Componeschi. Photo: Elin Lindström.

“We investigated phenotypes for different types of cells, i.e., differences in the cells’ expression of surface proteins, and I had the idea to add antibodies that recognize CD38. Suddenly, to my surprise, the B cells stopped dividing and secreting IgM antibodies. Now, five years later, it is my main focus and has resulted in a publication in a reputable journal,” says Alessandro Camponeschi, who is the first author of the article.

Important proteins

The current study shows that the cell surface protein CD38 is needed to activate the receptor, IgM-BCR, which leads to the production of the antibody IgM. Previously it has been suggested by other researchers that CD38 plays an important role in the activation of the receptor, which this study now demonstrates.

“When we blocked CD38 with an antibody or removed this molecule using the gene scissors CRISPR/Cas9, the connection between the receptor IgM-BCR and its co-receptor CD19 was inhibited. This impaired the signaling system that activates the IgM-BCR in both normal and malignant B cells,” says Alessandro, who is a researcher at the Department of Rheumatology and Inflammation at the Institute of Medicine.

Schematic model of the proposed localization and interaction of the surface molecules IgM, CD19 and CD38 in resting (no antigen) and stimulated (antigen) B cells, with and without exposure to anti-CD38 antibody treatment. Click to see a larger image.

New mechanism

In the study, the researchers also found that CD19, another protein that interacts with IgM-BCR, is located in the same small compartment on the B cell’s surface with CD38 and together they move close to the IgM-BCR upon pathogen recognition.

“We were able to show that the two molecules CD38 and CD19 sit very close to each other and move together when the IgM-BCR receptor is activated. Without either of these two proteins, the B cell is not activated.”

Relevant to cancer research

A large amount of CD38 is expressed in almost all forms of cancer involving B cells (multiple myeloma, lymphoma, and leukemia). Antibodies for the CD38 protein are already used in immunotherapy when treating multiple myeloma. The findings of this study indicate that antibodies against CD38 could be used as a treatment for other B cell malignancies, where these are driven by signaling via the IgM-BCR receptor.

One of the cancers where the findings are relevant is Burkitt’s lymphoma. It is a rare but very aggressive form of lymphoma that starts from mature B cells. When it comes to children, however, Burkitt’s lymphoma is one of the more common forms of cancer. In Sweden, around 15 children are struck by the disease each year. Variants of the disease are also significantly more common in countries around the equator.

“Research has made progress and treatments have improved. Many patients can become completely cancer-free from a combination of high-intensity cytostatics. But between ten and twenty percent of cases develop treatment resistance, so more drug options are needed.”

A pizza in Rome

Alessandro Componeschi. Photo: Elin Lindström.

Alessandro Camponeschi describes himself as a B cell geek; he is fascinated by B cells and the signaling pathways that control the cell’s behavior. He clearly remembers the event that steered him towards studying cell biology:

“I was working with pizza delivery at home in Rome that included delivering to a children’s hospital. Meeting the children with cancer stirred my desire to make a contribution to fight malignancies that affect children. I felt that I wanted to help.”

A few years later, he did his dissertation, also in Rome, and then applied to Gothenburg for the postdoctoral position in Lill Mårtensson-Bopp’s team.

“Lill is internationally renowned in the field of B cells, and the work in her team led to my own focus on B cells. She is also the last author of the work we have now published, says Alessandro, who now wants to establish his own research group.

Title: Human CD38 regulates B cell antigen receptor dynamic organization in normal and malignant B cells, Journal of Experimental Medicine; https://doi.org/10.1084/jem.20220201

To investigate whether IgM, CD19 and CD38 were close together, Alessandro Componeschi used a method called Fab-PLA, which is a modification of the proximity ligation assay (PLA). The method has been developed by Professor Michael Reth at the University of Freiburg, who is one of the study’s collaborators. Instead of whole antibodies, Fab-PLA uses only the Fab regions. With ordinary confocal microscopy, a resolution limit of 250nm is obtained in the co-localization analyses, while the resolution becomes significantly higher with PLA, which enables the study of the molecular interactions in the range of 10-20nm.

 

AV: ELIN LINDSTRÖM

By: Elin Lindström
Tagged With: avdelningen för reumatologi och inflammationsforskning, B-celler, Cancerforskning, grundforskning, institutionen för medicin, Ny studie, tidskriften Journal of Experimental Medicine, vetenskaplig publicering

HAPPY SUMMER!

The newsletter from Akademiliv will return on Wednesday, August 21st.

Contact your institute to add your event to the calendar in the Staff Portal

  • Biomedicine: Kristian Kvint: kalender@biomedicine.gu.se
  • Core Facilities: Amelie Karlsson: amelie.karlsson.2@gu.se
  • Clinical Sciences: Katarina Olinder Eriksson: klinvet@gu.se
  • Medicine: Nina Raun; kommunikation@medicine.gu.se
  • Neuroscience and Physiology: Josefin Bergenholtz; kommunikation@neuro.gu.se
  • Odontology: Johan Thompson; info@odontologi.gu.se
  • Sahlgrenska Academy’s Office and faculty-wide calendar events Åsa Ekvall; info@sahlgrenska.gu.se
  • Health and Care Sciences: Karin Mossberg; vardvetenskap@fhs.gu.se

Information from Sahlgrenska Academy Research Support Office

[UPDATED JUNE 2024]
The Sahlgrenska Academy Research Support Office provides an overview of upcoming and current calls, nominations and events in an information letter. This letter is updated on a monthly basis.
Current and previous newsletters are also available in the Staff Portal.

’20 minutes for researchers’ is back – see full spring program

During 20 minutes over Zoom, the Biomedical Library gives tips on tools and services that can facilitate your research everyday life.

More news

En personlig död (A Personal Death) – a chance to win Björn Fagerberg’s new book

27 May, 2024

NEW BOOK. During his career as a physician specializing in internal medicine, Björn Fagerberg has been involved in many end-of-life situations, …  

She is doing her residency in the US with a medical degree from Gothenburg

21 May, 2024

STUDENT. Doing a “residency” in orthopedics in the United States is an unattainable dream for many newly qualified American doctors. Now Janina Ka …  

Alba Corell reports from a high-level brain tumor meeting

20 May, 2024

COLUMN. The recent gathering of the Scandinavian Society of Neuro-oncology (SNOG) in Gothenburg has concluded. Professor Asgeir Jakola hosted and …  

From South Africa to Sweden: Collaborative Research Efforts Improving Pregnant Women’s Health

17 May, 2024

GLOBAL HEALTH. In the bustling Tygerberg University Hospital in Cape Town, a dedicated research team led by Lina Bergman, is on a mission to …  

Sara Bjursten and Anna Wenger are the recipients of the Assar Gabrielsson Prize 2024

17 May, 2024

AWARD. The Assar Gabrielsson Foundation has named Anna Wenger as the winner in the basic science research category and Sara Bjursten as the …  

A full day for PhD students focused on mental health

16 May, 2024

PHD STUDENTS. For the sixth time, PhD students at Sahlgrenska Academy were invited to PhD Day, organized by the Doctoral Student Council. The day …  

Kaj Blennow ranked highest in Sweden in neuroscience

16 May, 2024

AWARD. In this year's edition of the researcher ranking from Research.com in the field of neuroscience, Kaj Blennow is ranked 17th …  

Linda Wass is doing a postdoc at Stanford with ALF funding

14 May, 2024

ALF FUNDING. Biomedical Scientist Linda Wass has just settled in Stanford, California, where she will spend two years as a postdoc. She is the …  

Karin Nilsson wrote the Thesis of the Year at Sahlgrenska Academy in 2023

14 May, 2024

AWARD. Karin Nilsson, currently a postdoc at the Department of Internal Medicine and Clinical Nutrition, receives the faculty-wide Thesis of the …  

Some answers from the proposed members of the next Faculty Board

14 May, 2024

FACULTY ELECTIONS. The eight proposed members of the next Faculty Board hereby give some brief answers on how they want to contribute to the work …  

More news...

Sahlgrenska Academy

© University of Gothenburg
PO-Box 100, S-405 30 Gothenburg, Sweden
Phone: 00 46 31 786 0000

About the website

Elin Lindström is editor for Akademiliv.
Please feel free to send your ideas and comments to akademiliv@gu.se

Sign up for the Akademiliv newsletter:

Send you tips to Akademiliv

Do you have a suggestion for news, grants, seminars or an education?
Send an email to Elin Lindström Claessen