Role of CR2 in the human adult and neonatal in vitro antibody response to type 4 pneumococcal polysaccharide.
A number of studies have indicated that the complement receptor type 2 (CR2), which is the receptor for C3d, a degradation fragment of the complement component C3, regulates B lymphocyte activation and growth. Early reports have described that C3 regulates T cell-dependent (TD) antibody responses. The involvement of CR2 in the antibody response to T cell-independent type 2(TI-2) antigens was investigated because neonatal B cells, which are unresponsive to TI-2 antigens both in vivo and in vitro, express a significantly decreased level of CR2 as compared to B cells of adult donors. We utilized type 4 pneumococcal polysaccharide (PS4) as a model TI-2 antigen. In order to study the relationship between CR2 and the response to PS4, B cells were costimulated with PS4 and monoclonal antibodies (MAb) to CR2. HB5 and OKB7 anti-CR2 monoclonal antibodies enhanced the in vitro response of adult B cells to PS4, as measured in a PS4-specific spot-forming cell assay. Neonatal B cells could only be induced to respond to PS4 using high concentrations of OKB7 anti-CR2 MAb. The 8-mercaptoguanosine (8MGuo), an agent that can overcome the in vitro unresponsiveness to PS4 of neonatal B cells, increased CR2 expression on adult and neonatal B cells. Furthermore, 8MGuo synergizes strongly with anti-CR2 antibodies in augmenting the anti-PS4 antibody response. Data presented in this report provide evidence of CR2 involvement in the antibody response to PS4 and that the neonatal B cell unresponsiveness to TI-2 antigens may be due to the decreased expression of CR2.
Griffioen
A W
AW
Department of Immunology, University Children's Hospital, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
Toebes
E A
EA
Zegers
B J
BJ
Rijkers
G T
GT
D000328:Adult; D000917:Antibody Formation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000502:physiology; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015933:Complement C3d / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011951:Receptors, Complement / Q000032:analysis / Q000502:physiology*; D017464:Receptors, Complement 3d; D013296:Streptococcus pneumoniae / Q000276:immunology*
D000944:Antigens, Differentiation, B-Lymphocyte; D000955:Antigens, T-Independent; D011135:Polysaccharides, Bacterial; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D015933:Complement C3d