A role for gut-associated lymphoid tissue in shaping the human B cell repertoire.
We have tracked the fate of immature human B cells at a critical stage in their development when the mature B cell repertoire is shaped. We show that a major subset of bone marrow emigrant immature human B cells, the transitional 2 (T2) B cells, homes to gut-associated lymphoid tissue (GALT) and that most T2 B cells isolated from human GALT are activated. Activation in GALT is a previously unknown potential fate for immature human B cells. The process of maturation from immature transitional B cell through to mature naive B cell includes the removal of autoreactive cells from the developing repertoire, a process which is known to fail in systemic lupus erythematosus (SLE). We observe that immature B cells in SLE are poorly equipped to access the gut and that gut immune compartments are depleted in SLE. Thus, activation of immature B cells in GALT may function as a checkpoint that protects against autoimmunity. In healthy individuals, this pathway may be involved in generating the vast population of IgA plasma cells and also the enigmatic marginal zone B cell subset that is poorly understood in humans.
Blizard Institute and 2 Digestive Diseases Clinical Academic Unit, Barts and the London School of Medicine and Dentistry, Whitechapel, London, England, UK. a.vossenkaemper@qmul.ac.uk
Anna
A
Vossenkämper
Paul A
PA
Blair
Niloufar
N
Safinia
Louise D
LD
Fraser
Lisa
L
Das
Theodore J
TJ
Sanders
Andrew J
AJ
Stagg
Jeremy D
JD
Sanderson
Kirstin
K
Taylor
Fuju
F
Chang
Lee M
LM
Choong
David P
DP
D'Cruz
Thomas T
TT
Macdonald
Giovanna
G
Lombardi
Jo
J
Spencer
D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000473:pathology; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D054892:Metagenome / Q000276:immunology; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000473:pathology
D039641:Integrin beta Chains; C091368:integrin beta7