Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A.
J Exp Med
; 175(3): 671-82, 1992 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-1371300
ABSTRACT
In the present report, we have investigated the in vitro differentiation of surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to various stimuli. sIgD+ B cells homogeneously expressed some of the antigens identifying mantle zone B cells, but lacked expression of germinal center markers, thus confirming that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes. Conversely, sIgD- B cells expressed some of the antigens specifically associated with germinal center B cells. T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor beta (TGF-beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM, and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that ligation of CD40 was one of the obligatory signals required for commitment of naive B cells to IgA secretion. Limiting dilution experiments indicated that the IgA-potentiating effect of TGF-beta was due to its capacity to increase the frequency of IgA-producing cells, most likely as a consequence of class switching. Taken together, our data strongly suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina A Secretora
/
Linfócitos B
/
Antígenos de Diferenciação de Linfócitos B
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Antígenos CD
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Fator de Crescimento Transformador beta
/
Interleucina-10
/
Células Produtoras de Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
1992
Tipo de documento:
Article
País de afiliação:
França