Physiological-range temperature changes modulate cognate antigen processing and presentation mediated by lipid raft-restricted ubiquitinated B cell receptor molecules.
BCR-mediated Ag processing and presentation is critical to the initiation and control of a humoral immune response. Trafficking of internalized Ag-BCR complexes to intracellular Ag processing compartments is driven by ubiquitination of the cytoplasmic domain of the BCR. Using a biochemical approach, it is here established that ubiquitinated Ag-BCR complexes are formed via a signaling-dependent mechanism and restricted to plasma membrane lipid rafts. Because the structure of lipid rafts is temperature sensitive, the impact of physiological-range temperature changes (PRTCs; 33-39°C) on lipid raft-dependent and -independent BCR functions was investigated. Whereas the kinetics of lipid raft-independent BCR internalization is unaffected by temperature changes within this range, raft-dependent BCR signaling and ubiquitination as well as BCR-mediated Ag processing are significantly affected. The extent and duration of Ag-BCR ubiquitination is increased and prolonged at 37-39°C (normal to febrile temperature) compared with that at 33°C (peripheral body temperature). As might be expected, increased temperature also accelerates the overall kinetics of Ag-BCR degradation. Notably, at 33°C the expression of peptide-MHC class II complexes derived from the BCR-mediated processing of cognate Ag is profoundly slowed, whereas the kinetics of expression of peptide-MHC class II complexes derived from fluid-phase Ag processing remains unchanged. These results establish the effect of PRTCs on multiple lipid raft-dependent BCR functions including the processing and presentation of cognate Ag, suggesting one mechanism by which PRTCs, such as fever, may impact the initiation and/or maturation of a humoral immune response.
Katkere
Bhuvana
B
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Rosa
Sarah
S
Caballero
Adriana
A
Repasky
Elizabeth A
EA
Drake
James R
JR
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D021381:Protein Transport / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013696:Temperature; D057149:Ubiquitinated Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D054875:Ubiquitination
D011947:Receptors, Antigen, B-Cell; D057149:Ubiquitinated Proteins