Role of the major histocompatibility complex in T cell activation of B cell subpopulations. A single monoclonal T helper cell population activates different B cell subpopulations by distinct pathways.

It has recently been demonstrated that the Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirements for major histocompatibility complex (MHC)-restricted activation by T helper (TH) cells. To determine whether these MHC-restricted and -unrestricted pathways of B cell activation result from differences in the participating TH cell populations or reflect differences exclusively in the responding B cell subpopulations, experiments were carried out using cloned TH cells for in vitro antibody responses to trinitrophenyl-keyhole limpet hemocyanin. The same cloned T helper cells were able to activate both CBA/N (Lyb-5-) B cells and CBA/CaHN (Lyb-5+ + Lyb-5-) B cells under different experimental conditions. The activation of Lyb-5-B cells by cloned T helper cells required both MHC-restricted TH cell-B cell interaction and carrier-hapten linkage. In contrast, the activation of Lyb-5+ B cells required only MHC-restricted T helper cell interaction with accessory cells, while T-B interaction was MHC unrestricted and did not require carrier-hapten linkage. Thus, the differences in activation requirements observed for the Lyb-5- and Lyb-5+ B cell subsets do not result from differences in the TH cell populations activating these B cells, but rather reflect differences in the ability of these B cells to respond to signals from the same TH cells.

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Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

Journal of Experimental Medicine ◽

10.1084/jem.171.6.2153 ◽

1990 ◽

Vol 171 (6) ◽

pp. 2153-2158 ◽

Cited By ~ 44

Author(s):

J R Tumang ◽

D N Posnett ◽

B C Cole ◽

M K Crow ◽

S M Friedman

Keyword(s):

B Cells ◽

B Cell ◽

Mhc Class Ii ◽

Cell Activation ◽

Cell Interaction ◽

Class Ii ◽

B Cell Differentiation ◽

Th Cells ◽

Human B Cells ◽

Th Cell

Experimentally induced murine graft-vs.-host disease may be characterized by hypergammaglobulinemia, autoantibody formation, and immune complex-mediated organ system damage that mimics SLE. These autoimmune phenomena are mediated by abnormal Th-B cell cooperation, across MHC disparities, in which donor-derived allospecific Th cells recognize and interact with MHC class II antigens on the surface of recipient B cells. Microbial toxins, termed superantigens, which bind to MHC class II molecules and activate selected T cells based on TCR variable gene usage, may induce a similar form of Th-B cell interaction. In the present study, we generated and characterized human Th cell lines reactive with the Mycoplasma arthritidis superantigen (MAM). The essential observation is that resting human B cells bind MAM and present it to superantigen-reactive autologous or allogeneic Th cells, resulting in both Th cell activation and a consequent polyclonal Ig response by the superantigen-bearing B cells.

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Antigen-specific, MHC nonrestricted T helper cell-induced B cell activation.

Journal of Experimental Medicine ◽

10.1084/jem.164.5.1773 ◽

1986 ◽

Vol 164 (5) ◽

pp. 1773-1778 ◽

Cited By ~ 6

Author(s):

S M Friedman ◽

J A Jover ◽

E K Chartash ◽

M K Crow

Keyword(s):

B Cell ◽

Cell Activation ◽

Antigen Expression ◽

Cell Receptor ◽

Cell Interaction ◽

T Helper Cell ◽

B Cell Activation ◽

T Helper ◽

Th Cell ◽

Functional Nature

We used a cloned, TNP-specific, MHC-restricted, human Th cell line, E-11, and an assay of cognate Th-B cell interaction, BLAST-2 antigen expression on the B cell surface, to investigate the functional nature of the Th cell antigen receptor. We observed that E-11 induces BLAST-2 expression by resting B cells in a hapten-dependent, hapten-specific, but MHC nonrestricted manner. The implication of these results for the Th cell receptor are discussed.

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T cell regulation of b cell activation. Cloned Lyt-1+2-T suppressor cells inhibit the major histocompatibility complex-restricted interaction of T helper cells with B cells and/or accessory cells.

Journal of Experimental Medicine ◽

10.1084/jem.158.4.1178 ◽

1983 ◽

Vol 158 (4) ◽

pp. 1178-1190 ◽

Cited By ~ 41

Author(s):

Y Asano ◽

R J Hodes

Keyword(s):

Major Histocompatibility Complex ◽

B Cells ◽

Cell Activation ◽

Suppressor Cells ◽

Major Histocompatibility ◽

T Helper ◽

Th Cells ◽

Effector Cells ◽

Histocompatibility Complex ◽

Accessory Cells

The present studies have identified cloned Lyt-1+2- T suppressor (Ts) cells that are both antigen specific and major histocompatibility complex (MHC) restricted in their activation requirements and that function to regulate the MHC-restricted activation of B cells by T helper (Th) cells. ParentA-restricted Ts clones suppressed, in antigen-specific fashion, the responses generated by (A X B)F1 Th cells cooperating with parentA (B plus accessory) cells, but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B plus accessory) cells. Moreover, responses of (A X B)F1 leads to parentA Th cells and (A X B)F1 (B plus accessory) cells were suppressed by parentA-restricted Ts clones but not by parentB-restricted Ts clones. Thus, these findings suggest that the cloned Ts cells that have been characterized here function by specifically inhibiting the MHC-restricted interaction between Th cells and B and/or accessory cells. It was further demonstrated in experiments using cloned Th and Ts populations that these Lyt-1+2-Ts cells act not simply as inducers of suppressor but rather function in a restricted fashion as effector cells in the suppressor pathway.

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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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The histocompatibility restrictions on macrophage T-helper cell interaction determine the histocompatibility restrictions on T-helper cell B-cell interaction.

Journal of Experimental Medicine ◽

10.1084/jem.148.5.1171 ◽

1978 ◽

Vol 148 (5) ◽

pp. 1171-1185 ◽

Cited By ~ 37

Author(s):

U Yamashita ◽

E M Shevach

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

Cell Interaction ◽

T Helper Cell ◽

Helper T Cells ◽

T Helper ◽

Ia Antigens ◽

Nominal Antigen

To study the histocompatibility restriction between macrophages and helper T cells, carrier primed guinea pig T cells were positively selected in vitro with antigenpulsed macrophages for 7 days and the selected T cells were then mixed with hapten-primed B cells and stimulated with antigen in a modified Mishell-Dutton system. Helper T cells could only be selected with syngeneic, but not allogeneic, antigen-pulsed macrophages and would then collaborate only with syngeneic, but not allogeneic, hapten-primed spleen cells. When F1 T cells were selected with antigen-pulsed parental macrophages they would only collaborate with B cells of the same parental strain as the macrophages used in the selection culture. These results are strongly in support of the view that the primed T cell is activated by carrier determinants of the nominal antigen in association with Ia antigens on macrophages and the helper T cell, in turn, activates B cells which bear the same Ia antigens and determinants of the nominal antigen bound to immunoglobulin receptors on their surface. In addition, in experiments with antigens the response to which is controlled by I-linked genes, we demonstrated that primed (responder X nonresponder)F1 T cells would only collaborate with B cells of the responder parent. The defect appeared to be at the level of the B cell in that the addition to the cultures of antigen-presenting cells of the responder type did not restore the ability of F1 T cells to collaborate with non-responder B cells.

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Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.

Journal of Experimental Medicine ◽

10.1084/jem.158.2.265 ◽

1983 ◽

Vol 158 (2) ◽

pp. 265-279 ◽

Cited By ~ 31

Author(s):

K Bottomly ◽

B Jones ◽

J Kaye ◽

F Jones

Keyword(s):

T Cells ◽

B Cells ◽

Cell Surface ◽

B Cell ◽

Cell Activation ◽

Cell Surface Expression ◽

Th Cells ◽

Th Cell ◽

Ia Antigens

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.

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NKT-cell help to B lymphocytes can occur independently of cognate interaction

Blood ◽

10.1182/blood-2008-06-166249 ◽

2009 ◽

Vol 113 (2) ◽

pp. 370-376 ◽

Cited By ~ 72

Author(s):

Elena Tonti ◽

Grazia Galli ◽

Carmine Malzone ◽

Sergio Abrignani ◽

Giulia Casorati ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Cell Interaction ◽

Inkt Cells ◽

Th Cells ◽

Mhc Ii ◽

Th Cell ◽

Antibody Titers ◽

Antigen Presenting

Abstract CD4+ T (Th)–cell help to B lymphocytes requires cognate interaction and CD40 engagement. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that recognize αgalactosylceramide (αGalCer) presented by CD1d, and can help B-cell responses. We asked whether αGalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B–cell interaction. After immunization with protein Ags and αGalCer, antibody titers were assessed in wild-type or splenectomized mice, and in bone marrow radiation chimeras lacking CD1d or CD40 expression on B lymphocytes, or expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find that αGalCer-dependent enhancement of B-cell response (1) can occur when B cells do not express CD1d but express CD40; (2) requires that iNKT and Th cells interact with the same APCs that coexpress both CD1d and MHC-II; and (3) takes place without spleen. These findings demonstrate αGalCer-induced help for antibody responses can occur without cognate iNKT/B-cell interaction, and suggest this help entails activation of APCs by iNKT cells, which in turn activate Th cells and their helper functions for B cells. Thus, the αGalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses.

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T cell regulation of B cell activation. I-A-restricted T suppressor cells inhibit the major histocompatibility complex-restricted interactions of T helper cells with B cells and accessory cells.

Journal of Experimental Medicine ◽

10.1084/jem.157.6.1867 ◽

1983 ◽

Vol 157 (6) ◽

pp. 1867-1884 ◽

Cited By ~ 18

Author(s):

Y Asano ◽

R J Hodes

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

B Cells ◽

Cell Activation ◽

Cell Populations ◽

T Helper ◽

Th Cells ◽

Histocompatibility Complex ◽

Accessory Cells

The present studies were carried out to characterize the cellular interactions involved in the activation and function of the antigen-specific and antigen-nonspecific T suppressor (Ts) cells that regulate the IgG responses of Lyb-5-B cells. The in vitro activation of both Lyt-1+2- antigen-nonspecific Ts cells and Lyt-1-2+ antigen-specific Ts cells was shown to require the interaction of accessory cells and antigen-primed T cells. It was further demonstrated that this interaction was major histocompatibility complex (MHC)-restricted in that T cell recognition of I-A-encoded determinants on accessory cells was required for Ts cell activation. The activation of antigen-primed (A X B)F1 T cells with antigen in the presence of parentA or parentB accessory cells resulted, respectively, in the generation of parentA-restricted or parentB-restricted Ts cells. ParentA-restricted F1 Ts cells suppressed the responses generated by (A X B)F1 T helper (Th) cells cooperating with parentA (B + accessory) cells but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B + accessory) cells. Neither parentA-restricted Ts cells alone nor parentB-restricted Ts cells alone suppressed the responses of (A X B)F1 (B + accessory) cells, whereas a mixture of these two Ts cell populations was able to significantly suppress the responses of F1 (B + accessory) cells. In contrast, responses of (A X B)F1 leads to parentA Th cells (restricted to recognizing parentA but not parentB MHC determinants on F1 cells) and (A X B)F1 (B + accessory) cells was suppressed by parentA-restricted Ts cells but not by parentB-restricted Ts cells. Collectively these findings suggest that the Ts cell populations characterized here do not function by directly inhibiting the activity of Th cells, B cells or accessory cells of a given MHC genotype, but rather that they appear to function through a unique mechanism involving highly specific inhibition of the interaction between MHC-restricted Th cells and the (B + accessory) cells required for these responses.

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