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Surprising solution to an old problem

BIOSS researcher discovers the long sought ligand for the receptors on precursor B cells, Publication in Nature Immunology

Freiburg, 16.07.2010

Surprising solution to an old problem

The pre-B cell receptor (pre-BCR), a receptor that carries its own ligand.


Scientists from the Department of Molecular Immunology, Institute of Biology III, Faculty of Biology and the Centre for Biological Signalling Studies BIOSS have discovered a new mechanism that drives the development of B-lymphocytes in our bone marrow. B-lymphocytes are an important part of our immune system. Upon their activation they produce the antibodies protecting us from infections. Each day a human body produces 1 Billion (109) new B cells. Their development starts from hematopoietic stem cells and passes through a precursor B cell stage (pre-B cells) in the bone marrow where early B cells are expanded and selected. For their proper development pre-B cells require the expression and signalling function of the so-called pre-B cell receptor (pre-BCR). A failure to produce a functional pre-BCR results in the arrest of B cell development and a severe B cell immunodeficiency.

An older finding was that in contrast to the B cell antigen receptor (BCR) on mature B cells the pre-BCR is constitutively signalling on pre-B cells. This initiated a search for the ligand of this receptor that was assumed to be expressed by other cells of the bone marrow environment. However, it also had been found earlier that the pre-BCR retained its constitutive signalling even on isolated pre-B cells. The group headed by Dr. Hassan Jumaa has now found a solution to this long standing puzzle. They discovered that the pre-BCR carries its own ligand in form of a sugar group attached to the heavy chain of the receptor. Specifically, they showed that by genetically removing this particular glycogroup the pre-BCR is losing its continuous signalling behaviour. “Finding the ligand as part of the pre-BCR is somewhat like finding a treasure in your front garden that everybody else was hunting in remote parts of the world“ says Rudolf Uebelhart, the first author of the publication and a PhD student funded by the Spemann Graduate School of Biology and Medicine (SGBM).



Nature Immunology: Autonomous pre-BCR function requires a specific N-linked glycosylation site in the heavy chain.

Rudolf Übelhart, Martina P. Bach, Cathrin Eschbach, Thomas Wossning, Michael Reth and Hassan Jumaa

Published online: July 17, 2010


Christiane Gieseking-Anz




Dr. Hassan Jumaa
Department of Molecular Immunology, Faculty of Biology
Excellence cluster, Centre for Biological Signalling Studies, BIOSS,
University of Freiburg and
Max Planck Institute of Immunobiology, Germany
Tel: +49-761-5108-437/4210