P70W1-2 Schistosome infection stimulates host CD4^+ T helper cell and B cell responses against a novel egg antigen thioredoxin peroxidase

Major histocompatibility complex-restricted helper T cell clones against "minor" antigens expressed on B cell and macrophage surfaces, when confronted with appropriate T cell-depleted spleen cells, are induced to proliferation and, in turn, activate "target-responder" B cells to polyclonal growth and maturation. Irradiation of helper cell populations, however, demonstrates that their effector functions (and B lymphocyte responses) are independent of proliferative activity. Adherent cell depletion on Sephadex G10 columns, while completely abrogating helper T cell proliferation, does not abolish helper cell-induced B cell responses, demonstrating a remarkable quantitative difference in macrophage requirements for the growth of these two cell types. Because significant B cell responses are detected upon interaction with primed helper T cells under conditions of extreme macrophage depletion, we conclude that the role of macrophages in T-B cell cooperation is limited to expansion of optimal numbers of helper T lymphocytes. It follows that activated helper cells can autonomously produce all B cell-specific growth and maturation factors mediating cooperative antibody responses. In contrast, the profound reduction of LPS-induced responses upon macrophage depletion suggests accessory cell production of such factors in thymus-independent B cell growth and/or maturation.

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Schistosome Infection Stimulates Host CD4+ T Helper Cell and B-Cell Responses against a Novel Egg Antigen, Thioredoxin Peroxidase

Infection and Immunity ◽

10.1128/iai.69.2.1134-1141.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 1134-1141 ◽

Cited By ~ 47

Author(s):

David L. Williams ◽

Hiroko Asahi ◽

Douglas J. Botkin ◽

Miguel J. Stadecker

Keyword(s):

B Cell ◽

Interleukin 2 ◽

Granuloma Formation ◽

T Helper ◽

Cell Responses ◽

Th Cell ◽

Thioredoxin Peroxidase ◽

Ifn Γ ◽

B Cell Responses ◽

Egg Antigen

ABSTRACT Egg granuloma formation during schistosome infections is mediated by CD4+ T helper (Th) cells sensitized to egg antigens; however, most of the relevant sensitizing egg antigens are still unknown. Here we show that schistosome thioredoxin peroxidase (TPx)-1 is a novel T- and B-cell egg antigen in schistosome-infected mice. CD4+ Th cell responses to fractionated egg components identified a significant response against a 26-kDa antigen; a partial amino acid sequence of this antigen was found to be identical to that of Schistosoma mansoni TPx-1. The native TPx-1 elicited significant proliferative responses as well as gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-5 secretion in CD4+ cells from 8.5-week-infected CBA and C57BL/6 mice. By comparison, recombinant TPx-1 elicited a smaller, more type 1-polarized response, with significant production of IFN-γ and IL-2, less IL-5, and essentially no IL-4. In C57BL/6 mice the responses to TPx-1 were relatively more prominent than that directed against the major egg antigen, Sm-p40, whereas in CBA mice the reverse was true. B-cell responses were also monitored in infected C57BL/6, C3H, CBA, and BALB/c mice. All strains had significant antibody levels against the TPx-1 protein, but the most significant antibody production ensued following parasite oviposition. TPx-1 was localized in eggs and shown to be secreted by eggs. The identification of egg antigens is important to understand the specific basis of granuloma formation in schistosome infections and may prove to be useful in strategies to ameliorate pathological responses.

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Requirement for three signals in B cell responses. II. Analysis of antigen- and Ia-restricted T helper cell-B cell interaction.

Journal of Experimental Medicine ◽

10.1084/jem.156.2.415 ◽

1982 ◽

Vol 156 (2) ◽

pp. 415-429 ◽

Cited By ~ 40

Author(s):

R H Zubler ◽

O Kanagawa

Keyword(s):

B Cells ◽

B Cell ◽

Cell Interaction ◽

T Helper Cell ◽

Helper Cell ◽

B Cell Differentiation ◽

T Helper ◽

Cell Level ◽

Cell Responses ◽

Helper Factor

We have recently reported that resting B cells must receive at least three different signals in a T helper cell (TH)-dependent as well as in a lipopolysaccharide (LPS)-induced B cell response (3), i.e., a specific TH signal (that can be bypassed by LPS), a nonspecific TH signal (mediated by Ia or antigen-nonspecific B cell helper factor), and an antigen (hapten) signal. In a system using male (H-Y) antigen-specific cloned TH of C57BL/6 origin and male (or female) B cells, we now confirm and extend these findings by demonstrating that H-Y-specific TH must see both H-Y and Ia determinants on the B cells (and not only on macrophages) to provide the first specific TH signal required for a plaque-forming cell (PFC) response. This signal was interfered with by a monoclonal anti-I-Ab antibody at the B cell level, was not mediated by detectable soluble factors (in contrast to the nonspecific signal also provided by the TH), and could be bypassed by LPS, in which case anti-I-Ab antibody had no effect. However, although the H-Y-specific TH induced a polyclonal PFC response (B cell differentiation) in the apparent absence of an antigen seen by the B cells, significant clonal expansion of PFC precursors occurred only when the B cells also recognized an antigen (hapten).

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