Anti-renin T cells trigger normal B cells to produce anti-renin antibodies and normalize blood pressure in spontaneously hypertensive rats.
Spontaneously hypertensive (SH) rats immunized with mouse renin produce anti-renin antibodies, responsible for down-modulation of blood pressure, associated with an infiltration of kidneys by mononuclear cells. In this work, anti-renin T cells from SH rats immunized with renin have been stimulated in vitro, and we have studied in vitro and in vivo their effect on anti-renin antibody production by normal syngeneic B cells. We show that, in vitro, renin-activated T cells induce a renin-specific antibody response without addition of exogenous renin. Anti-renin T cells injected into naive SH rats trigger normal B cells to secrete high amounts of monospecific anti-renin IgG antibodies as early as day 5. These antibodies interfere with the homeostasis of the renin-angiotensin system leading to the normalization of blood pressure without any nephritis. These results show that anti-renin B cells are either not tolerant per se or in a reversible state of anergy. Our results also suggest that anti-renin B cells constitutively express renin-derived peptides in such a way that they may be stimulated by activated anti-renin T cells; these cells express IL-4 mRNA indicating that IL-4 could play a role in the differentiation of B cells.
Castedo
M
M
INSERM U28, Hôpital Broussais, Paris, France.
Pelletier
L
L
Pasquier
R
R
Guettier
C
C
Huygen
K
K
Michel
J B
JB
Druet
P
P
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006973:Hypertension / Q000201:enzymology / Q000628:therapy*; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D007371:Interferon-gamma; D010047:Ovalbumin; D012083:Renin