Immature B cell homing shapes human lymphoid tissue structure and function

Abstract

Shortly after the emergence of newly formed human B cells from bone marrow as transitional cells, they diverge along two developmental pathways that can be distinguished by the level of IgM they express and migratory biases. Here, we propose that differential tissue homing of immature B cell subsets contributes to human lymphoid tissue structure and function.

Figure 1.

Recruitment of immature B cells to lymphoid tissues. B cells exit the bone marrow as T1 B cells, expressing high levels of IgM and CD10. Their transition to T2 cells is characterized by a reduction in CD10 expression and gain of CD21, with two distinct developmental pathways becoming apparent. T2 IgM^hi cells selectively express α4β7 integrin, which mediates homing to GALT and spleen through binding to its cognate receptor MAdCAM-1. T2 IgM^lo cells express relatively more L-selectin and are thus enriched in their potential to enter lymphoid tissues expressing its ligand PNAd, including lymph nodes and tonsils. We propose that T2 IgM^hi and T2 IgM^lo cells mature into MZB and naïve B cells, respectively. Higher receptor surface expression may enable IgM^hi cells to respond to multivalent repeated subunit antigens that drive TI responses. IgM^lo cells are instead adapted to T-dependent responses to single epitope antigens.

Figure 2.

Features of lymphoid tissues with contrasting recruitment biases. (A–F) Images in A–F were acquired by imaging mass cytometry analysis of normal human spleen (A and D), appendix (B and E), and tonsils (C and F) to illustrate the previously described features of tissues seeded by T2 IgM^hi (A, B, D, and E) or T2 IgM^lo cells (C and F). Images in A, B, and C illustrate B cells (CD20⁺, green), T cells (CD3⁺, magenta), epithelium (E-cadherin⁺, white), and endothelium (CD31⁺, cyan). GALT (A) and spleen (B) are relatively rich in B cells in comparison with tonsils (C) and have a well-defined microanatomical marginal zone on the periphery of the B cell follicle. In each case, the GC contains proliferating cells (Ki-67⁺, red). Tonsils have a relatively greater abundance of T cells compared with GALT or splenic white pulp (C compared to A and B). Lymphocyte subtypes in tonsils are biased toward naïve cells, as indicated by fewer T cells expressing CD45RO (cyan) and relatively more naïve B cells expressing IgD (red) compared with GALT and spleen (F compared to D and E). MZ = marginal zone; Ma = mantle zone of naïve cells.