Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is differentially expressed during human B cell differentiation and inhibits B cell receptor-mediated signaling.
Leukocyte-associated Ig-like receptor-1 (LAIR-1) belongs to the growing family of immunoreceptor tyrosine-based inhibitory motif-bearing receptors and is expressed on the majority of peripheral mononuclear cells, including NK cells, T cells, B cells, monocytes, and dendritic cells. In this study, we investigated the distribution and the capacity of LAIR-1 to function as an inhibitory receptor on human B cells. LAIR-1 is expressed from early on during B cell differentiation, but is absent on approximately half of the memory B cells, and all germinal center B cells, plasmablasts, and terminally differentiated plasma cells. In vitro stimulation of naive B cells via the B cell receptor (BCR) or CD40, triggering proliferation and differentiation into Ig-producing plasma cells, is accompanied by loss of LAIR-1 expression. We previously reported that LAIR-1 can function as an inhibitory receptor on NK cells and T cells. Here, we demonstrate that it can also function as a negative regulator of BCR-mediated signaling, since simultaneous cross-linking of LAIR-1 and the BCR reduces the increase of intracellular Ca(2+) evoked by BCR ligation. Taken together, this suggests that the inhibitory mechanism of LAIR-1 is functional in multiple components of the hematopoietic system.
van der Vuurst de Vries
A R
AR
Department of Immunology, University Hospital Utrecht, Utrecht, The Netherlands.
Clevers
H
H
Logtenberg
T
T
Meyaard
L
L
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1