Long-sought ligand for receptors on precursor B cells discovered

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 one billion 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 signaling 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 signaling 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 signaling 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 loosing its continuous signaling 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 Speeman graduate school of Biology and Medicine (SGBM).