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Characterization and expression of H-21 region gene products on bone marrow-derived macrophages
Abstract:
Antigen-presenting macrophages (M phi) were derived from day 7 cultures of bone marrow stem cells using L cell conditioned medium. The adherent bone marrow-derived macrophages (BMM phi) were 100% esterase-positive, 95% positive for C3 receptors, 93% positive for Fc receptors, and 95% actively phagocytic. Indirect immunofluorescence using anti-Ia monoclonal antibodies resulted in 60% Ia-positive BMM phi on day 7 of stem cell culture. BMM phi could stimulate mixed lymphocyte reaction (MLR) proliferation across an I-A subregion difference, but not across I-J subregion differences. This contrasted with splenic M phi which stimulated MLR proliferation across both an I-A and I-J subregion difference. The apparent lack of I-J subregion determinants on BMM phi correlated with their ability to function as antigen-presenting cells. In these experiments, BMM phi effectively reconstituted the trinitrophenyl-specific IgM plaque-forming cell (PFC) response of B cells but not the primary burro red blood cell (BRBC)-specific IgM-PFC response of M phi-depleted spleen cells. When BMM phi were added to BRBC-primed T and B cells, they reconstituted the secondary IgG PFC response to levels obtained using splenic M phi. These experiments relate the differential expression of H-21 region determinants on antigen-presenting cells with their functional capacity.
Insights
Bone marrow-derived macrophages (BMM phi) show differential expression of MHC class II determinants, impacting their antigen-presenting cell function. This study highlights how specific H-21 region determinants influence macrophage capabilities in immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophages are crucial antigen-presenting cells (APCs) involved in initiating adaptive immune responses.
- The expression of MHC class II molecules on APCs is critical for T cell activation.
- Bone marrow-derived macrophages (BMM phi) are a valuable model for studying macrophage function.
Purpose of the Study:
- To investigate the expression of Ia and I-J subregion determinants on BMM phi.
- To evaluate the functional capacity of BMM phi as APCs in mixed lymphocyte reactions (MLRs) and B cell responses.
- To correlate the differential expression of H-21 region determinants with APC function.
Main Methods:
- Derivation of BMM phi from bone marrow stem cells.
- Characterization of BMM phi using esterase staining, C3 and Fc receptor analysis, and phagocytosis assays.
- Assessment of Ia expression on BMM phi via indirect immunofluorescence.
- Functional assays including MLR stimulation and B cell reconstitution for IgM and IgG plaque-forming cell (PFC) responses.
Main Results:
- BMM phi exhibited high phagocytic activity and expression of C3 and Fc receptors.
- Approximately 60% of BMM phi were Ia-positive, but they lacked I-J subregion determinants.
- BMM phi stimulated MLR proliferation across I-A but not I-J subregion differences, unlike splenic macrophages.
- BMM phi effectively reconstituted T cell-dependent B cell responses (TNP-specific IgM PFC) and secondary IgG PFC responses.
Conclusions:
- The differential expression of H-21 region determinants, specifically the lack of I-J determinants, on BMM phi influences their APC function.
- BMM phi can act as effective APCs for certain immune responses, particularly those involving B cell activation.
- These findings underscore the relationship between MHC molecule expression and the functional specialization of antigen-presenting cells.