Antigen recognition. V. Requirement for histocompatibility between antigen-presenting cell and B cell in the response to a thymus-dependent antigen, and lack of allogeneic restriction between T and B cells.

We examined the effects of the developmental milieu on the capacity of B cells to undergo immune response gene-controlled, T cell-dependent polyclonal proliferation. Although I-Aq poly(Glu60 Ala30 Tyr10)n (GAT)-nonresponder T cells developing in a responder environment become phenotypic GAT-responders, I-Aq B cells remain unresponsive to GAT, even after maturation in a GAT-responder animal. Conversely, (B10.A x B10.Q)F1 ([GAT responder x GAT nonresponder]F1) T cells developing in a B10.Q GAT nonresponder host fail to respond to GAT, but F1 B cells from the same F1 leads to parent chimeras make excellent proliferative responses in the presence of GAT and responder T cells. Thus, by this assay, B cell immune response gene function is genetically determined and is not affected by the developmental milieu.

Section: H-2 Axq H-2 ~ ~ H-2 Axq H-2 ~Q ~ H-2 ~ and H-2 ~Q ~ H-2 Qsupporting

confidence: 86%

B lymphocyte immune response gene phenotype is genetically determined.

Tse¹,

Mond²,

Longo³

1982

“…Although such complex recognition is characteristic of T cell specificity, there have been reports that imunoglobulins can also be restricted to the recognition of certain antigenic determinants in the context of cell surface antigens (10,11). Similarly, although many studies have indicated that B cell stimulation need not be haplotype restricted (4,(27)(28)(29), a few recent investigations have implied that under certain conditions B cells may only be stimulated by antigen presented in the context of cells of an appropriate H-2 haplotype (12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, antigen-specific cytolytic T lymphocytes are restricted in effector function by the major histocompatibility complex (MHC) 1 of the stimulatory antigen-bearing cells (6)(7)(8)(9). Such recognition, which apparently dominates the T cell specificity repertoire, has recently been implicated in antigen recognition by B cells as well (10)(11)(12)(13)(14)(15). However, because many antibodies can bind to antigens in the absence of presenting cells, the portion of antibody binding that may be dependent on antigen presentation in the context of a presenting cell may generally be obscured by antibodies in the population capable of binding the antigen per se.…”

mentioning

confidence: 99%

Participation of the major histocompatibility complex in antibody recognition of viral antigens expressed on infected cells.

Wylie¹,

Sherman²,

Klinman³

1982

The capacity of the antibody repertoire to recognize complex antigens on viral-infected cells was investigated at the level of monoclonal B cell responses. A majority of primary B cells responsive to PR8(H1N1)-infected H-2 syngeneic cells produced antibody that bound viral determinants only in the context of infected cells and not the isolated virion. An examination of the fine specificity of such antibodies revealed that most could be distinguished by a panel of cells infected with closely related heterologous H1 influenza strains. Indeed, most antibodies bound hemagglutinin determinants of PR8 exclusively, and few were broadly cross-reactive. An examination of the same antibodies for their recognition of cell surface antigens revealed that the majority recognized MHC-encoded antigenic determinants. Thus, most BALB.K (H-2k) primary B cells responsive to PR8-L919 (H-2k) cells produced monoclonal antibodies that bound PR8-antigens only in the context of H-2Dk-infected cells. Most C57BL/10 (H-2b) B cells responsive to PR8-EL4 (H-2b) cells produced monoclonal antibodies that bound PR8 antigens only in the context of H-2Kb-infected cells. These latter antibodies were further shown to recognize that H-2Kb molecule by virtue of their capacity to be discriminated by a panel of PR8-infected H-2Kb mutant cells. These findings demonstrate that much of the antibody repertoire is capable of highly specific complex recognition of viral antigenic determinants in the context of the appropriate MHC alloantigen.

“…It has recently been demonstrated (12)(13)(14)(15)) that B cells, as well as TH cells, can express requirements for recognition of self-MHC determinants expressed by the accessory cells with which they interact. In particular, it has recently been shown (15) that B cells from long-term radiation bone marrow chimeras express a requirement for MHC-restricted self-recognition in TI responses to high concentrations of TNPFicoll.…”

Section: Discussionmentioning

confidence: 99%

Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-Ficoll. A novel cell interaction pathway requiring self-recognition of accessory cell H-2 determinants by both T cells and B cells.

Hodes¹,

Hathcock²,

Singer³

1983

In vitro primary antibody responses to limiting concentrations of trinitrophenyl (TNP)-Ficoll were shown to be T cell dependent, requiring the cooperation of T helper (TH) cells, B cells, and accessory cells. Under these conditions, TH cells derived from long-term radiation bone marrow chimeras were major histocompatibility complex (MHC) restricted in their ability to cooperate with accessory cells expressing host-type MHC determinants. The requirement for MHC-restricted self-recognition by TNP-Ficoll-reactive B cells was assessed under these T-dependent conditions. In the presence of competent TH cells, chimeric B cells were found to be MHC restricted, cooperating only with accessory cells that expressed host-type MHC products. In contrast, the soluble products of certain monoclonal T cell lines were able to directly activate B cells in response to TNP-Ficoll, bypassing any requirement for MHC-restricted self-recognition. These findings demonstrate the existence of a novel cell interaction pathway in which B cells as well as TH cells are each required to recognize self-MHC determinants on accessory cells, but are not required to recognize each other. They further demonstrate that the requirement for self-recognition by B cells may be bypassed in certain T-dependent activation pathways.