Newly produced virgin B cells migrate to secondary lymphoid organs but their capacity to enter follicles is restricted

Lortan, J.; Roobottom, Carl; Oldfield, Susan; MacLennan, Ian C. M.

doi:10.1002/eji.1830170914

Cited by 69 publications

(42 citation statements)

References 18 publications

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“…Experiments in which bone marrow Bcells were transferred into congenic strains of rats differing in x L chain allotype indicate that at least a proportion of these cells migrate to the Tcell-rich zones (TZ) of secondary lymphoid tissues and the red pulp (Rp) of the spleen. Only limited numbers of these cells, however, pass on to the follicular mantles (FM) [15].…”

Section: Introductionmentioning

confidence: 99%

Only a small proportion of splenic B cells in adults are short‐lived virgin cells

Chan

MacLennan

1993

Eur J Immunol

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A cohort of newly produced virgin B cells was followed from the marrow to the spleen of non-immunized clean rats, which showed minimal antigen-driven proliferation of B cells in their spleens. The progenitors of this cohort of virgin cells were labeled in vivo over 12 h with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd) and their non proliferating progeny left the marrow 2-3 days later. This coincided with the arrival of labeled B cells in the red pulp and T zones of the spleen. These appear to be short-lived as few remained a week after the label was given. The short-lived newly produced virgin B cells can only comprise a minority of splenic B cells, for it is shown that only 20% of splenic B cells are found in the red pulp and T zone. It is calculated that newly produced virgin B cells are likely to make up between 5% and 10% of splenic B cells. In the marginal zones and follicular mantle respective medians of 3.3% and 1.8% were already labeled at 1 day from the start of the BrdUrd pulse. The appearance of these cells seems likely to result from antigen-driven B cell proliferation outside the marrow, for labeled virgin B cells have not started to leave the marrow at this stage. During day 2 and 3 the proportion of labeled follicular mantle B cells rose to 3.4%, which might in part reflect the recruitment of newly produced virgin B cells to the pool of recirculating follicular B cells. After day 3 in the follicles and day 1 in the marginal zones the proportion of labeled cells did not vary significantly through day 7. This appears to confirm the comparative longevity of the cells in these zones, which contain 80% of the non-proliferating splenic B cells of adult rats.

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Section: Introductionmentioning

confidence: 99%

Only a small proportion of splenic B cells in adults are short‐lived virgin cells

Chan

MacLennan

1993

Eur J Immunol

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“…4,14 These immature B cells then penetrate the marginal zone sinus and reside in the outer zone of the periarteriolar lymphoid sheath (PALS), 15 where they become part of the B-cell-rich follicular areas. 15,16 At this site in the spleen, B cells are still immature and can be distinguished from their mature counterparts. 4,14,17 The transition from immature to mature B cell is characterized by a series of changes in surface marker expression and the activities of these B cells.…”

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Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration

Flaishon

Becker-Herman

Hart

et al. 2004

Blood

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In the bone marrow, B-cell development can be divided into different stages according to the rearrangement status of the immunoglobulin H (IgH) and IgL chain loci 1,2 and the expression of intracellular and surface-bound markers. The first cells expressing IgM at their surface during this developmental process are the immature B cells, 3 which leave the bone marrow and migrate to the spleen for their final maturation. 4,5 One of the most fundamental and important aspects of the immune system is its ability to recognize and respond to virtually any foreign antigen while maintaining strict unresponsiveness to self-antigens. For B cells, antigens encountered during the immature stage are likely to be self-antigens, and reactive clones are, therefore, subjected to negative selection through deletion, [6][7][8] receptor editing, 9,10 and anergy. 11 The selection process occurring within the immature B-cell compartments is also extended to the periphery, allowing deletion of virtually all B cells recognizing peripheral self-antigens outside of the bone marrow. 12 Immature B cells leave the bone marrow and migrate to the spleen where they can mature prior to antigen encounter. Like other naive lymphocytes, before their arrival in the spleen immature B cells might recirculate to nonsplenic secondary lymphoid organs, which are specialized tissues for collecting antigens, 13 or to sites of infection and inflammation. In these secondary lymphoid organs, where differentiation to mature cells does not occur, antigen encounter would lead to the death of the immature B cells and elimination of effective clones because of the negative selection process. Thus, it is imperative for B cells to home to the spleen and undergo a splenic maturation step before their release into the periphery.Homing of immature B cells to the spleen proceeds through the terminal branches of central arterioles to blood sinusoids of the marginal zone. 4,14 These immature B cells then penetrate the marginal zone sinus and reside in the outer zone of the periarteriolar lymphoid sheath (PALS), 15 where they become part of the B-cell-rich follicular areas. 15,16 At this site in the spleen, B cells are still immature and can be distinguished from their mature counterparts. 4,14,17 The transition from immature to mature B cell is characterized by a series of changes in surface marker expression and the activities of these B cells.Two populations of splenic B cells were recently identified as precursors of mature cells. Transitional B cells of type 1 (T1) are the recent immigrants from the bone marrow. Migrating T1 cells expressing B-cell receptors (BCRs) with high affinity to soluble self-antigens (Ags) in the blood are likely to die by negative selection by way of Ag-induced death. On entry to the spleen, T1 cells remain at the PALS, where additional bloodborne self-Ags trapped by the spleen may further drive negative selection. The remaining T1 cells develop into transitional B cells of type 2 (T2), which are found exclusively in the primary follicles of th...

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“…The first cells expressing IgM at their surface during this developmental process are the immature B cells that leave the bone marrow and migrate to the spleen (3, 4). These immature B cells then penetrate the marginal zone sinus and reside in the outer zone of the periarteriolar lymphocytic sheath (5), where they become part of the B cell-rich follicular areas (5,6). At this site in the spleen, B cells are still immature and can be distinguished from their mature counterparts (3,(7)(8)(9).…”

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confidence: 99%

Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity

Matza

Lantner

Bogoch

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Early stages of B cell development take place in the bone marrow, resulting in formation of immature B cells, which migrate to the spleen for their final differentiation into mature cells. This final maturation step is essential for B cells to become responsive to antigens and to participate in the immune response. Previously, we showed that the MHC class II chaperone, invariant chain (Ii), controls the differentiation of B cells from the immature to the mature stage. In this study, by generating transgenic mice expressing truncated Ii lacking its luminal domain, we could dissect the chaperonin activity of Ii from its role in B cell maturation. We demonstrate in vivo that Ii N-terminal domain is directly involved in the maturation of B cells and is sufficient to promote B cell differentiation.transgenic mice ͉ N-terminal domain ͉ immature B cell ͉ mature B cell ͉ antigen presentation B cell development involves the ordered progression of a stem cell through a number of stages, ultimately resulting in a mature B cell. There are various selective criteria that the cell must fulfill to complete this program. In the bone marrow, B cell development can be divided into different stages, based on the rearrangement status of the IgH and IgL chain loci (1, 2) and the expression of intracellular and surface-bound markers. This developmental program is controlled largely by a set of transcription factors and signaling pathways. The first cells expressing IgM at their surface during this developmental process are the immature B cells that leave the bone marrow and migrate to the spleen (3, 4). These immature B cells then penetrate the marginal zone sinus and reside in the outer zone of the periarteriolar lymphocytic sheath (5), where they become part of the B cell-rich follicular areas (5, 6). At this site in the spleen, B cells are still immature and can be distinguished from their mature counterparts (3,(7)(8)(9). The transition from immature to mature B cells is characterized by a series of changes in surface marker expression and in the activities of these cells. Recently, this transition stage was characterized further and divided into two populations. Transitional B cells of type 1 (T1) are the recent immigrants from the bone marrow. These cells develop into transitional B cells of type 2 (T2), which cycle and are found exclusively in the primary follicles of the spleen (10). Only 5-10% of the newly generated immature B cells are selected into the pool of long-lived, antigen-responsive mature B cells (9, 11). Why and how only such a small proportion of immature B cells is selected and by what molecular mechanism this selection occurs are largely unknown.Previously, we have shown that invariant chain (Ii), a MHC class II chaperone, plays a crucial role in B cell maturation (12). MHC class II molecules are heterodimeric complexes that present foreign antigenic peptides on the cell surface of antigenpresenting cells (APCs) to CD4 ϩ T cells (13)(14)(15). MHC class II synthesis and assembly begin in the endoplasmic reticul...

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Newly produced virgin B cells migrate to secondary lymphoid organs but their capacity to enter follicles is restricted

Cited by 69 publications

References 18 publications

Only a small proportion of splenic B cells in adults are short‐lived virgin cells

Only a small proportion of splenic B cells in adults are short‐lived virgin cells

Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration

Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity

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