A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

Anna Vossenkämper; Paul A Blair; Niloufar Safinia; Louise D Fraser; Lisa Das; Theodore J Sanders; Andrew J Stagg; Jeremy D Sanderson; Kirstin Taylor; Fuji Chang; Lee M Choong; David D’Cruz; Thomas T Macdonald; Giovanna Lombardi; Jo Spencer

doi:10.1084/jem.20122465

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

Anna Vossenkämper, Paul A Blair, Niloufar Safinia, Louise D Fraser, Lisa Das, Theodore J Sanders, Andrew J Stagg, Jeremy D Sanderson, Kirstin Taylor, Fuji Chang, Lee M Choong, David D’Cruz, Thomas T Macdonald, Giovanna Lombardi, Jo Spencer

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Abstract

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.

Original language	English
Pages (from-to)	1665-1674
Number of pages	10
Journal	Journal of Experimental Medicine
Volume	210
Issue number	9
DOIs	https://doi.org/10.1084/jem.20122465
Publication status	Published - 12 Aug 2013

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Vossenkämper, A., Blair, P. A., Safinia, N., Fraser, L. D., Das, L., Sanders, T. J., Stagg, A. J., Sanderson, J. D., Taylor, K., Chang, F., Choong, L. M., D’Cruz, D., Macdonald, T. T., Lombardi, G., & Spencer, J. (2013). A role for gut-associated lymphoid tissue in shaping the human B cell repertoire. Journal of Experimental Medicine, 210(9), 1665-1674. https://doi.org/10.1084/jem.20122465

@article{feb917330d9440f490b157b7c203f93c,

title = "A role for gut-associated lymphoid tissue in shaping the human B cell repertoire",

abstract = "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.",

author = "Anna Vossenk{\"a}mper and Blair, {Paul A} and Niloufar Safinia and Fraser, {Louise D} and Lisa Das and Sanders, {Theodore J} and Stagg, {Andrew J} and Sanderson, {Jeremy D} and Kirstin Taylor and Fuji Chang and Choong, {Lee M} and David D{\textquoteright}Cruz and Macdonald, {Thomas T} and Giovanna Lombardi and Jo Spencer",

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Vossenkämper, A, Blair, PA , Safinia, N , Fraser, LD, Das, L, Sanders, TJ, Stagg, AJ, Sanderson, JD, Taylor, K, Chang, F, Choong, LM, D’Cruz, D, Macdonald, TT, Lombardi, G & Spencer, J 2013, 'A role for gut-associated lymphoid tissue in shaping the human B cell repertoire', Journal of Experimental Medicine, vol. 210, no. 9, pp. 1665-1674. https://doi.org/10.1084/jem.20122465

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AU - Vossenkämper, Anna

AU - Blair, Paul A

AU - Safinia, Niloufar

AU - Fraser, Louise D

AU - Das, Lisa

AU - Sanders, Theodore J

AU - Stagg, Andrew J

AU - Sanderson, Jeremy D

AU - Taylor, Kirstin

AU - Chang, Fuji

AU - Choong, Lee M

AU - D’Cruz, David

AU - Macdonald, Thomas T

AU - Lombardi, Giovanna

AU - Spencer, Jo

PY - 2013/8/12

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N2 - 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.

AB - 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.

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DO - 10.1084/jem.20122465

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JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

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ER -

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

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