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The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment.

Abstract：

:It has been shown that in xenotransplantation of human cells into immunodeficient mice, the mouse strain background is critical. For example, the nonobese diabetic (NOD) strain is most efficient, the BALB/c is moderate, and the C57BL/6 is inefficient for human cell engraftment. We have shown that the NOD-specific polymorphism of the signal regulatory protein-alpha (Sirpa) allows NOD SIRPA to bind human CD47, and the resultant "don't eat me" signaling by this binding prevents host macrophages to engulf human grafts, thereby inhibiting rejection. Here we tested whether the efficient xenotransplantation capability of the BALB/c strain is also mediated by the SIRPA-CD47 self-recognition system. BALB/c SIRPA was capable of binding to human CD47 at an intermediate level between those of C57BL/6 SIRPA and NOD SIRPA. Consistent with its binding activity, BALB/c-derived macrophages exhibited a moderate inhibitory effect on human long-term culture-initiating cells in in vitro cultures, and showed moderate phagocytic activity against human hematopoietic stem cells. The increased affinity of BALB/c SIRPA for human CD47 was mounted at least through the BALB/c-specific L29V SNP within the IgV domain. Thus, the mouse strain effect on xenogeneic engraftment might be ascribed mainly to the binding affinity of strain-specific polymorphic SIRPA with human CD47. This information should be useful for developing a novel immunodeficient strain with superior efficiency for xenogeneic transplantation of human cells.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Iwamoto C,Takenaka K,Urata S,Yamauchi T,Shima T,Kuriyama T,Daitoku S,Saito Y,Miyamoto T,Iwasaki H,Kitabayashi I,Itoh K,Kishimoto J,Kohda D,Matozaki T,Akashi K

doi

10.1016/j.exphem.2013.11.005

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

163-171.e1

issue

3

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(13)00864-3

journal_volume

42

pub_type

杂志文章

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