Abstract: Provided herein is a heavy chain constant region comprising a CH1 domain, a hinge region, a CH2 domain and a CH3 domain, wherein the sequences of said CH1 domain and hinge region derive from the sequences of CH1 domain and hinge region in human IgG2, the sequences of said CH2 domain and CH3 domain derive from the sequences of CH2 domain and CH3 domain in human IgGs; and wherein, said antibody heavy chain constant region has an affinity to human Fc?RIIB equal to or higher than the affinity of human IgG1 to human Fc?RIIB, said antibody heavy chain constant region has an I/A ratio equal to or higher than human IgG1 has. Also provided are antibodies or fusion proteins based on a heavy chain constant region according to the above, wherein the antibody heavy chain constant region significantly enhances agonistic activity of the antibodies or fusion proteins and improves efficacy of the antibodies or fusion proteins in treating diseases like tumors and autoimmune diseases.