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

1982 ◽  
Vol 156 (2) ◽  
pp. 415-429 ◽  
Author(s):  
R H Zubler ◽  
O Kanagawa

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).

1982 ◽  
Vol 156 (2) ◽  
pp. 350-360 ◽  
Author(s):  
Y Asano ◽  
M Shigeta ◽  
C G Fathman ◽  
A Singer ◽  
R J Hodes

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.


1983 ◽  
Vol 157 (1) ◽  
pp. 312-323 ◽  
Author(s):  
A Bandeira ◽  
G Pobor ◽  
S Petterson ◽  
A Coutinho

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.


1978 ◽  
Vol 148 (5) ◽  
pp. 1171-1185 ◽  
Author(s):  
U Yamashita ◽  
E M Shevach

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.


Haematologica ◽  
2010 ◽  
Vol 96 (1) ◽  
pp. 78-86 ◽  
Author(s):  
K. Ait-Tahar ◽  
A. P. Liggins ◽  
G. P. Collins ◽  
A. Campbell ◽  
M. Barnardo ◽  
...  

1990 ◽  
Vol 141 (4) ◽  
pp. 427-430
Author(s):  
M.K. Crow ◽  
S.M. Friedman

1989 ◽  
Vol 170 (3) ◽  
pp. 877-886 ◽  
Author(s):  
J C Cambier ◽  
K R Lehmann

One of the most controversial questions in immunology is the molecular basis by which Th lymphocytes deliver activating signals to quiescent B lymphocytes during T cell-dependent immune responses. Recent studies suggest that T cell-dependent activation of quiescent B lymphocytes may involve signaling mediated by direct T helper cell-B cell contact. Since B cell membrane-associated MHC-encoded class II molecules (Ia) must be recognized by Th lymphocytes for generation of T cell-dependent humoral immune responses, they are obvious candidates for receptors of this signal. Here we report that stimulation of quiescent murine B cells with IL-4 and antibodies against the B cell antigen receptor for 12-16 h primes cells to proliferate in response to immobilized mIa binding ligands. In the presence of additional lymphokines, these B cells differentiate to secrete Ig of IgM and IgG classes. These results suggest that Ia molecules are receptors for direct, T helper cell-B cell contact mediated signaling that results in B cell proliferation.


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