CD93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche.
Plasma cells represent the end stage of B-cell development and play a key role in providing an efficient antibody response, but they are also involved in numerous pathologies. Here we show that CD93, a receptor expressed during early B-cell development, is reinduced during plasma-cell differentiation. High CD93/CD138 expression was restricted to antibody-secreting cells both in T-dependent and T-independent responses as naive, memory, and germinal-center B cells remained CD93-negative. CD93 was expressed on (pre)plasmablasts/plasma cells, including long-lived plasma cells that showed decreased cell cycle activity, high levels of isotype-switched Ig secretion, and modification of the transcriptional network. T-independent and T-dependent stimuli led to re-expression of CD93 via 2 pathways, either before or after CD138 or Blimp-1 expression. Strikingly, while humoral immune responses initially proceeded normally, CD93-deficient mice were unable to maintain antibody secretion and bone-marrow plasma-cell numbers, demonstrating that CD93 is important for the maintenance of plasma cells in bone marrow niches.
Chevrier
Stéphane
S
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Genton
Céline
C
Kallies
Axel
A
Karnowski
Alexander
A
Otten
Luc A
LA
Malissen
Bernard
B
Malissen
Marie
M
Botto
Marina
M
Corcoran
Lynn M
LM
Nutt
Stephen L
SL
Acha-Orbea
Hans
H
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D002454:Cell Differentiation; D002645:Chickens; D051740:Ikaros Transcription Factor; D007114:Immunization; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011951:Receptors, Complement / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology; D053668:Syndecan-1 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D005719:gamma-Globulins / Q000276:immunology
C491396:Ikzf3 protein, mouse; D008562:Membrane Glycoproteins; C513258:Prdm1 protein, mouse; D011951:Receptors, Complement; D053668:Syndecan-1; D015534:Trans-Activators; D014157:Transcription Factors; C032402:complement 1q receptor; D005719:gamma-Globulins; D051740:Ikaros Transcription Factor; D000074462:Positive Regulatory Domain I-Binding Factor 1