Functional properties of membrane-associated complement receptor CR1
Insights
Membrane receptors for C3b (CR1) on lymphocytes inhibit complement activation. These CR1 molecules, along with others on the cell surface, act as local inhibitors of the complement cascade.
Area of Science:
- Immunology
- Complement System Biology
Background:
- Membrane receptors for C3b (CR1) from human erythrocytes are known inhibitors of the complement cascade.
- CR1 encompasses regulatory functions similar to serum proteins beta 1H (H) and C4-binding protein (C4bp).
Purpose of the Study:
- To investigate the functional properties of membrane-associated CR1 on lymphocytes.
- To determine the role of CR1 in inhibiting complement activation on lymphocyte membranes.
Main Methods:
- Incubation of tonsil lymphocytes with complement intermediates (EAC14oxy2lim or EAC14oxy23lim).
- Assessing inhibitory effects using dose-dependent assays, mild trypsinization, and formaldehyde-fixed cells.
- Utilizing monoclonal antibodies to CR1 and fluid phase C3b to reverse inhibitory effects.
- Observing the release of C3c fragments upon addition of C3b-inactivator (I) and assessing the role of CR1 in this process.
Main Results:
- Lymphocytes bearing CR1 inhibit complement intermediates C42 and C423 in a dose-dependent manner.
- Inhibitory effects are mediated by membrane-associated molecules and are retained in fixed cells.
- CR1 partially mediates the inhibitory effects, with approximately 60% reversal by anti-CR1 antibodies or fluid phase C3b.
- Lymphocytes release C3c fragments from EAC14oxy23b upon addition of C3b-inactivator, a process abolished by anti-CR1 antibodies.
Conclusions:
- Membrane-associated CR1 on lymphocytes functions as an inhibitor of complement activation.
- Other lymphocyte membrane molecules may also contribute to complement inhibition.
- These findings support the role of CR1 and associated membrane proteins in regulating complement activity in their local environment.
Abstract:
It was previously shown that membrane receptors for C3b (CR1) purified from human erythrocytes were powerful inhibitors of the complement cascade and that they encompass the regulatory functions of the serum proteins beta 1H (H) and C4-binding protein (C4bp). In the present report we study the functional properties of membrane-associated CR1. When tonsil lymphocytes, which contain between 30 and 60% of CR1-bearing B cells, are incubated with the red cell complement intermediate EAC14oxy2lim or EAC14oxy23lim, they inhibit both C42 and C423 in a dose-dependent manner. These effects are mediated by membrane-associated molecules. Indeed, mild trypsinization of the lymphocytes abolishes their activity, and formaldehyde-fixed cells are as effective as viable cells. The inhibitory effects are in part mediated by CR1. The lymphocyte activities are reversed about 60% if monoclonal antibodies to CR1 or fluid phase C3b are present in the incubation medium. Moreover, upon addition of C3b-inactivator (l), lymphocytes release C3c fragments from EAC14oxy23b. The release of C3c was also abolished by antibodies to CR1. These results support the idea that CR1, as well as other molecules from the lymphocyte membrane, can function as inhibitor(s) of complement activation in their vicinity.
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