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N E Phillips

Publications and source records attributed to N E Phillips.

26 records · Page 2Linked to original sources
PubMed1985

Subclass specificity of Fc gamma receptor-mediated inhibition of mouse B cell activation.

We have shown previously that cross-linking receptors for the Fc of IgG (Fc gamma R) to membrane Ig will inhibit membrane Ig-dependent mouse B cell activation. In this report we have determined which mouse IgG subclasses will mediate this inhibition by using monoclonal mouse anti-p-azophenylarsonate (anti-ars) antibodies to inhibit B cell activation by arsanilated rabbit Fab'2 anti-mouse IgM (arsFab'2 anti-mu). Cell recovery and Ig secretion after 4 days of culture with soluble helper factors and arsFab'2 anti-mu was inhibited by IgG1, IgG2b, and IgG2a anti-ars, but not IgM or Fab'2 anti-ars. In addition, we determined which of the inhibitory IgG subclasses are blocked by the monoclonal anti-mouse Fc gamma R antibody 2.4G2, which we have previously shown prevents inhibition by rabbit IgG anti-mu. These experiments demonstrated that 2.4G2 Fab could block inhibition mediated by IgG2a as well as that mediated by IgG1 and IgG2b. Because it has been reported that 2.4G2 does not bind the IgG2a receptor on macrophages, these data support our previous experiments, which indicated that this inhibition is not macrophage dependent.

Animals↗
PubMed1984

Cross-linking of B lymphocyte Fc gamma receptors and membrane immunoglobulin inhibits anti-immunoglobulin-induced blastogenesis.

The Fc portion of rabbit anti-mouse immunoglobulin (Ig) antibodies interferes with anti-Ig-induced B lymphocyte activation as measured by DNA synthesis on day 3 of culture or maturation to Ig-secreting cells in the presence of soluble helper factors on day 4 or 5. To investigate this Fc-dependent effect at an earlier stage in B cell activation, rabbit IgG anti-mouse mu-chain- or delta-chain-specific antibodies were compared with their F(ab')2 fragments for the ability to induce mouse B cells to undergo blast transformation, as defined by an increase in cell volume during the first 24 hr of culture. Both F(ab')2 anti-Ig reagents induce blast transformation, although F(ab')2 anti-mu antibodies induce a greater size change than F(ab')2 anti-delta antibodies. Whole anti-mu or anti-delta antibodies do not induce blast transformation; however, in the presence of a monoclonal anti-mouse Fc gamma receptor antibody that blocks IgG binding to Fc gamma receptors (Fc gamma R), whole anti-mu or anti-delta antibodies induce blast transformation as well as their F(ab')2 fragments. Because the anti-Fc gamma R antibody alone has no effect on blast transformation, it appears that the simultaneous binding of membrane IgM (or IgD) and Fc gamma R by whole anti-Ig antibodies prevents this early event in membrane Ig-induced B cell activation.

Animals↗
PubMed1983

Fc-dependent inhibition of mouse B cell activation by whole anti-mu antibodies.

We have been using whole rabbit anti-mouse mu antibodies to study Fc-dependent inhibition of mouse B cell activation by F(ab')2 anti-mu antibodies and antigen-nonspecific helper factors (SN). We show here that this inhibition does not appear to require adherent cells, appears to occur independently of cellular interactions, is reversible, and is not maintained solely by suppressive factors. In addition, occupancy of Fc receptors by rabbit antibody-antigen complexes is not sufficient to inhibit activation by F(ab')2 anti-mu and SN. These observations, in conjunction with the observation that blocking the Fc receptor-binding capacity of rabbit anti-mu antibodies by protein A prevents inhibition, suggest that cross-linking mlg and Fcgamma receptors on B cells prevents activation. However, the F(ab')2 anti-mu and SN-activated B cells become refractory to this inhibition by 48 hr in culture.

Animals↗
PubMed1981

Antigen-primed helper T cell function in CBA/N mice is radiosensitive.

CBA/N mice have an X-linked immunodeficiency that includes a deficient humoral response to sheep red blood cells (SRBC). In order to study the cellular mechanisms of this deficiency we have examined helper T cell function to SRBC in an adoptive transfer system by using 2 different sources of helper T cells. When thymocytes were used as the source of helper T cell precursors in an adoptive transfer system, CBA/N thymocytes were as effective as CBA/Ca thymocytes in inducing CBA/Ca bone marrow cells to develop into both direct and indirect anti-SRBC plaque-forming cells (PFC). However, when SRBC-primed, irradiated recipient mice were used as the source of helper T cells, primed and irradiated CBA/N recipients developed significantly fewer direct and indirect anti-SRBC PFC than similarly treated CBA/Ca recipients when reconstituted with CBA/Ca bone marrow cells and challenged with SRBC. This difference in radioresistant helper T cell function was also observed when primed, irradiated (CBA/N X DBA/2)F1 defective male and nondefective female mice were used as recipients of F1 female bone marrow cells and SRBC, confirming that this defect is a part of the X-linked CBA/N immunodeficiency. This deficiency in radioresistant helper T cell function in CBA/N mice does not appear to be due either to suppressor T cell function, or to a negative effect of the CBA/N environment on either B cell maturation, T cell-B cell cooperation, or helper T cell function. We conclude that antigen-primed helper T cell function in CBA/N mice is radiosensitive. Possible reasons for this are evaluated and discussed.

Animals↗
PubMedDate not supplied

Induction of immunological tolerance to islet allografts.

T-cell dependent activation of resting B cells involves the interaction of gp39 on T cells with its receptor, CD40, on B cells. We administered either a combination of T-cell-depleted splenic lymphocytes and anti-gp39 monoclonal antibody or antibody alone to establish islet allografts in mice without continuous immunosuppression. Fully allogeneic H-2q FVB islets were permanently accepted by chemically diabetic H-2b C57BL/6 mice provided that the recipients were pretreated with both T-cell-depleted donor spleen cells and anti-gp39 antibody. Antibody alone was less effective in prolonging allograft survival, but we did observe that anti-gp39 mAb alone can exert an independent, primary effect on islet allograft survival that was dose dependent. Targeting gp39, in combination with lymphocyte transfusion, might prove suitable for tolerance induction and allotransplantation without immunosuppression.

Animals↗