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      Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7

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          Abstract

          Progression of HIV disease is associated with the appearance of numerous B cell defects. We describe herein a population of immature/transitional B cells that is overly represented in the peripheral blood of individuals with advancing HIV disease. These B cells, identified by the expression of CD10, were unresponsive by proliferation to B cell receptor triggering and possessed a phenotype and an Ig diversity profile that confirmed their immature/transitional stage of differentiation. Consistent with an immature status, their lack of proliferation to B cell receptor triggering was reversed with CD40 ligand, but not B cell activation factor. Finally, levels of CD10 expression on B cells were directly correlated with serum levels of IL-7, suggesting that increased levels of IL-7 modulate human B cell maturation either directly or indirectly by means of a homeostatic effect on lymphopenia. Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events.

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          Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

          A Fauci, Joanne Edgar, Robert G. Whalen … (1983)
          We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.
          Article 0 comments Cited 141 times – based on 0 reviews     Review now
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            The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance.

            Terry Fry, Crystal Mackall (2005)
            IL-7 is well known as a lymphopoietic cytokine, but recent studies have also identified a critical role for IL-7 in peripheral T cell homeostasis. IL-7 is well poised to serve as a homeostatic cytokine because it is produced by resting stromal cells, the IL-7R is present on most T cells, and IL-7 down-regulates its own receptor. These features allow IL-7 to signal large numbers of resting T cells and to be efficiently used when supplies are limiting. Consistent with this, in normal hosts, IL-7 is required for survival of naive T cell populations, and IL-7 contributes to homeostatic cycling of naive and memory cells. In addition, lymphopenic hosts accumulate increased levels of IL-7, and the supranormal levels are largely responsible for inducing homeostatic peripheral expansion in response to lymphopenia. Thus, IL-7 plays critical and nonredundant roles in both T cell lymphopoiesis and in maintaining and restoring peripheral T cell homeostasis.
            Article 0 comments Cited 137 times – based on 0 reviews     Review now
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              Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation.

              W E DeMuth, Susan Shinton, D Allman … (2001)
              Although immature/transitional peripheral B cells may remain susceptible to selection pressures before full maturation, the nature and timing of these selection events remain unclear. We show that correlated expression of surface (s) IgM (sIgM), CD23, and AA4 defines three nonproliferative subpopulations of immature/transitional peripheral B cells. We designate these populations transitional (T) 1 (AA4(+)CD23(-)sIgM(high)), T2 (AA4(+)CD23(+)sIgM(high)), and T3 (AA4(+)CD23(+)sIgM(low)). Cells within all three subsets are functionally immature as judged by their failure to proliferate following sIgM cross-linking in vitro, and their rapid rate of turnover in vivo as assessed by 5-bromo-2'-deoxyuridine labeling. These labeling studies also reveal measurable cell loss at both the T1-T2 and T2-T3 transitions, suggesting the existence of multiple selection points within the peripheral immature B cell pool. Furthermore, we find that Btk-deficient (xid) mice exhibit an incomplete developmental block at the T2-T3 transition within the immature B cell pool. This contrasts markedly with lyn(-/-) mice, which exhibit depressed numbers but normal ratios of each immature peripheral B cell subset and severely reduced numbers of mature B cells. Together, these data provide evidence for multiple selection points among immature peripheral B cells, suggesting that the B cell repertoire is shaped by multiple unique selection events that occur within the immature/transitional peripheral B cell pool.
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                Author and article information

                Journal
                Title: Proceedings of the National Academy of Sciences
                Abbreviated Title: PNAS
                Publisher: Proceedings of the National Academy of Sciences
                ISSN (Print): 0027-8424
                ISSN (Electronic): 1091-6490
                Publication date Created: February 14 2006
                Publication date Created: February 14 2006
                Publication date (Print): February 14 2006
                Publication date (Electronic): February 06 2006
                Volume: 103
                Issue: 7
                Pages: 2262-2267
                Article
                DOI: 10.1073/pnas.0511094103
                PMC ID: 1413756
                PubMed ID: 16461915
                SO-VID: 4955c419-620a-4499-8578-ba3364d5f665
                Copyright © © 2006
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