A role for gut-associated lymphoid tissue in shaping the human B cell repertoire.
1665 - 1674
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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.
AuthorsVossenkämper, A; Blair, PA; Safinia, N; Fraser, LD; Das, L; Sanders, TJ; Stagg, AJ; Sanderson, JD; Taylor, K; Chang, F; Choong, LM; D'Cruz, DP; Macdonald, TT; Lombardi, G; Spencer, J
- College Publications